Publications by authors named "Guowei Zuo"

27 Publications

  • Page 1 of 1

Integrated bioinformatic analysis and experiment confirmation of the antagonistic effect and molecular mechanism of ginsenoside Rh2 in metastatic osteosarcoma.

J Pharm Biomed Anal 2021 Jul 19;201:114088. Epub 2021 Apr 19.

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

This study aimed to compare the gene expression variation of clinical primary osteosarcoma (OS) and metastatic OS, identify expression profiles and signal pathways related to disease classification, and systematically evaluate the potential anticancer effect and molecular mechanism of ginsenoside Rh2 on OS. A raw dataset (GSE14359), which excluded GSM359137 and GSM359138, was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and principal component analysis (PCA) were obtained with limma. Pathways enrichment analysis was understood by GSEA app. Rh2-associated targets were harvested and mapped through PharmMapper and Cytoscape 3.4.0. The toxicity of Rh2 was determined using crystal staining and MTT assay on 143B and MG63 cell lines. The relative protein expression was confirmed through Western blot analysis. The mitochondrial membrane potential (△Ψm) was evaluated by JC-1 fluorescence staining. The cell mobility was measured via wound healing and transwell assays. A total of 752 genes were upregulated, while 161 genes were downregulated. GSEA and PCA displayed significant function enrichment and classification. Through PharmMapper and Cytoscape 3.4.0, Rh2 was found to target the mitogen activated protein kinase (MAPK) and PI3K signaling pathways, which are the key pathways in the metastasis of OS. Furthermore, Rh2 induced a concentration-dependent decrease in cell viability and early apoptosis associated with ΔΨm decline, while a non-lethal dose of Rh2 weakened the metastatic capability. Moreover, systematic evaluation showed that promoting the MAPK signaling pathway and inhibiting PI3K/Akt/mTOR were correlated with the anticancer effects of Rh2 on metastatic OS. In conclusion, transcriptome-derived approaches may be beneficial in diagnosing early metastases, and Rh2, a multi-targeting agent, shows promising application potential in suppressing metastatic OS in an MAPK- and PI3K/Akt/mTOR-dependent manner.
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http://dx.doi.org/10.1016/j.jpba.2021.114088DOI Listing
July 2021

Ginsenoside Rg3 Inhibits the Growth of Osteosarcoma and Attenuates Metastasis through the Wnt/-Catenin and EMT Signaling Pathway.

Evid Based Complement Alternat Med 2020 11;2020:6065124. Epub 2020 Jul 11.

Key Laboratory of Laboratory Medical Diagnostics of Ministry of Education, Chongqing Medical University, Chongqing 400016, China.

Osteosarcoma (OS) is the most common primary malignant bone cancer. An increasing number of studies have demonstrated that ginsenoside Rg3 (Rg3), which is extracted from the roots of the traditional Chinese herb Panax ginseng, plays a tumor suppression role in various malignant tumors. In the present study, we aimed at investigating the role of Rg3 in the proliferation, migration, and invasion of OS and at exploring the underlying mechanisms. Cell viability and proliferation were observed by MTT assay and crystal violet staining. The migration and invasion of cells were measured by wound-healing assay and Transwell method. Signaling pathway screening was investigated using luciferase reporter gene assay. qRT-PCR and western blot were performed to measure the expression of molecules involved in cell epithelial-mesenchymal transition (EMT), and Wnt/-catenin pathway. Results suggested that Rg3 could not only inhibit proliferation but also hamper the migration and invasion of OS. qRT-PCR and western blot demonstrated that a reduced level of MMP2/MMP7/MMP9 was induced after Rg3 treatment. In addition, the expression levels of proteins related to EMT and the Wnt/-catenin pathway were downregulated. In summary, our data revealed that Rg3 could inhibit the proliferation, migration, and invasion of OS cells. This effect of Rg3 might be mediated by downregulating MMP2, MMP7, and MMP9 expression and suppressing EMT as well as the Wnt/-catenin pathway. Thus, Rg3 might be a potential agent for the treatment of OS.
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http://dx.doi.org/10.1155/2020/6065124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369650PMC
July 2020

Nucleus-located PDK1 regulates growth, invasion and migration of breast cancer cells.

Life Sci 2020 Jul 26;253:117722. Epub 2020 Apr 26.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address:

Aims: It is well known that pyruvate dehydrogenase kinase 1 (PDK1) is highly expressed in breast cancer (BC) tissues and promotes tumor growth, but the underlying mechanisms of this process are unclear. Here, we investigated the effects of nuclear PDK1 on growth, migration and invasion in human BC cells.

Main Methods: The sub-cellular localization of PDK1 in BC cells was performed with subcellular fractionation followed by Western blot and immunofluorescence. The localization of PDK1 in breast normal tissue and breast duct carcinoma was detected by Immunohistochemistry. Then the protein-protein interaction between PDK1 and Importin β was verified by co-immunoprecipitation assay. Finally, the effects of nuclear PDK1 on cell proliferation, apoptosis, migration and invasion of BC cells were assessed.

Key Findings: In addition to its well-known sub-cellular localization, PDK1 was present in the nucleus of BC cells, and EGF treatment increased nucleus distribution of PDK1. Moreover, the level of nuclear PDK1 accumulation facilitated the growth of BC cells. We also found that the entry of PDK1 into nucleus mainly relied on the nuclear localization signal (NLS), and NLS mutation inhibited the entry of PDK1 into nucleus; as a result, the migration and invasion abilities of BC cells were impaired, and the number of apoptotic cells was significantly increased.

Significance: Our findings provided a new supplement to the sub-cellular localization of PDK1 in BC cells and uncovered the function of nuclear PDK1 in facilitating BC cells growth, migration and invasion.
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http://dx.doi.org/10.1016/j.lfs.2020.117722DOI Listing
July 2020

The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma.

Oncol Rep 2020 Feb 31;43(2):491-502. Epub 2019 Dec 31.

Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.

MicroRNA‑708‑5p (miR‑708‑5p) and epithelial‑​to‑mesenchymal transition (EMT) have been widely identified to contribute to the pathogenesis and progression of multiple cancers. However, the connection between miR‑708‑5p and EMT has not been sufficiently clarified. Therefore, our research aimed to investigate the impact of miR‑708‑5p on EMT and the metastasis of osteosarcoma (OS). We first analyzed the differentially expressed microRNAs (DEmiRNAs) from the GSE70367 dataset. We found that the expression of miR‑708‑5p was lower in OS cells. Overexpression of miR‑708‑5p was able to impair the migration and invasion of OS cells. Moreover, miR‑708‑5p inhibited EMT of OS cells MG63 and SaOS‑2, wherein E‑cadherin was increased, and N‑cadherin, vimentin, and Snail were decreased. Semaphorin 4C (SEMA4C), mitogen‑activated protein kinase kinase kinase 3 (MAP3K3), and zinc finger E‑box‑binding homeobox 1 (ZEB1) were predicted as target genes of miR‑708‑5p by bioinformatics method. Only ZEB1, one of the EMT‑inducing transcription factors, was validated as the direct target gene of miR‑708‑5p in OS cells through dual‑luciferase reporter assay and Western blot analysis. Knockdown of ZEB1 was found to inhibit the metastasis of MG63 and SaOS‑2 cells, whereas ZEB1 over-expression promoted their metastasis. In summary, miR‑708‑5p impaired the metastasis and EMT of OS, which was found to be mediated by inhibition of ZEB1.
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http://dx.doi.org/10.3892/or.2019.7452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967104PMC
February 2020

Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes.

Aging (Albany NY) 2019 12 12;11(23):11520-11540. Epub 2019 Dec 12.

Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.

Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD . Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD.
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http://dx.doi.org/10.18632/aging.102552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932923PMC
December 2019

Long non-coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes.

J Cell Mol Med 2020 01 6;24(2):1399-1412. Epub 2019 Dec 6.

Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long non-coding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up-regulated in oleic acid-induced steatosis and during the development of high-fat diet (HFD)-induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up-regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up-regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19-induced lipid accumulation in hepatocytes. Furthermore, H19-induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF-04691502. Accordingly, H19 overexpression in hepatocytes up-regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up-regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these findings strongly suggest that H19 may play an important role in regulating hepatic lipid metabolism and may serve as a potential therapeutic target for NAFLD.
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http://dx.doi.org/10.1111/jcmm.14818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991647PMC
January 2020

Dentinogenesis and Tooth-Alveolar Bone Complex Defects in Knockout Mice.

Stem Cells Dev 2019 05 2;28(10):683-694. Epub 2019 Apr 2.

1 Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, China.

Tooth development is regulated by sequential and reciprocal epithelium-mesenchymal interactions and their related molecular signaling pathways, such as bone morphogenetic proteins (BMPs). Among the 14 types of BMPs, BMP9 (also known as growth differentiation factor 2) is one of the most potent BMPs to induce osteogenic differentiation of mesenchymal stem cells. The purpose of this study was to examine potential roles of BMP9 signaling in tooth development. First, we detected the expression pattern of BMP9 in tooth germ during postnatal tooth development, and we found that BMP9 was widely expressed in odontoblasts, ameloblasts, dental pulp cells, and osteoblasts in alveolar bones. Then, we established a -KO mouse model. Gross morphological examination revealed that the tooth cusps of -KO mice were significantly abraded with shorter roots. Micro-computed tomography and three-dimensional reconstruction analysis indicated that the first molars of the -KO mice exhibited a reduced thickness dentin, enlarged pulp canals, and shortened roots, resembling the phenotypes of the common hereditary dental disease dentinogenesis imperfecta. Further, the alveolar bone of the -KO mutants was found to be shorter and had a decreased mineral density and trabecular thickness and bone volume fraction compared with that of the wild-type control. Mechanistically, we demonstrated that both dentin sialophosphoprotein and dentin matrix protein 1 were induced in dental stem cells by BMP9, whereas their expression was reduced when BMP9 was silenced. Further studies are required to determine whether loss of or decreased BMP9 expression is clinically associated with dentinogenesis imperfecta. Collectively, our results strongly suggest that BMP9 may play an important role in regulating dentinogenesis and tooth development. Further research is recommended into the therapeutic uses of BMP9 to regenerate traumatized and diseased tissues and for the bioengineering of replacement teeth.
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http://dx.doi.org/10.1089/scd.2018.0230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534167PMC
May 2019

Synergistic antitumor effect of suberoylanilide hydroxamic acid and cisplatin in osteosarcoma cells.

Oncol Lett 2018 Oct 27;16(4):4663-4670. Epub 2018 Jul 27.

Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.

Cisplatin, as a first-line chemotherapy drug, has been widely applied for therapy of osteosarcoma. However, its application is limited by drug resistance and serious side effects, including nephrotoxicity and ototoxicity. Suberoylanilide hydroxamic acid (SAHA) is a newly developed histone deacetylase (HDAC) inhibitor, which is the first Food and Drug Administration-approved HDAC inhibitor for the treatment of cutaneous manifestations of T-cell lymphoma. However, SAHA as a monotherapy was revealed to be limited, particularly in solid tumors. In the present study, 143B osteosarcoma cells were treated with multiple concentrations of SAHA or cisplatin, either alone or combined. The morphological characteristics of the treated cells were observed using an inverted microscope. The cytotoxicity effects of the combination of SAHA and cisplatin on 143B cells were analyzed by MTT assay, colony formation assay, wound healing cell migration assay, cell apoptosis assay and cell cycle analysis. Western blot analysis was performed to detect the protein expression levels of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, cleaved-caspase-3, cleaved-caspase-8 and cleaved-poly (ADP-ribose) polymerase (PARP). The experimental data indicated that the inhibition of cell proliferation in the combination group was significantly increased compared with that in single drug groups. Expression levels of pro-apoptotic protein were upregulated, whereas anti-apoptotic Bcl-2 was downregulated significantly in 143B cells following SAHA/cisplatin treatment. Taken together, the results revealed that the combination of SAHA and cisplatin inhibited the proliferation of 143B cells and induced their apoptosis synergistically, and this effectiveness may be mediated by caspase activation.
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http://dx.doi.org/10.3892/ol.2018.9224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126343PMC
October 2018

Biological analysis of cancer specific microRNAs on function modeling in osteosarcoma.

Sci Rep 2017 07 14;7(1):5382. Epub 2017 Jul 14.

Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Yuzhong district, Chongqing, 400016, China.

Osteosarcoma (OS) is the most common bone tumor characterized with a high risk of amputation and malignant morbidity among teenagers and adolescents. However, relevant pathogenic/biological mechanisms underlying OS-genesis remains to be ambiguous. The aim of this study was to elucidate functional relationship about microRNAs-mRNAs networks and to identify potential molecular markers via a computational method. Gene expression profile (GSE70415) was recruited from Gene Expression Omnibus. 3856 differentially expressed genes and 250 significantly expressed microRNAs were identified by using GCBI. The results of GO and KEGG pathways associated proteomics analysis indicated that extracellular matrix organization, small molecule metabolic process, cell adhesion (GO IDs: 0030198, 0044281, 0007155) and pathways in cancer, PI3K-Akt signaling pathway, metabolic pathways (pathway IDs: 5200, 4151, 1100) were significantly enriched. In addition, CKMT2, miR-93b-5p, miR-29b-3p were found to be positively/negatively correlated with TP53, EGFR, and MMP members mediated OS development, including angiogenesis, migration and invasion. Further visualization of collective effect of 1181 microRNAs-mRNAs pairs and protein-protein interactions was realized by applying with cytosacpe. In summary, our work provided a better understanding of non-coding regulatory mechanisms of transcriptomics and unraveled essential molecular biomarkers in osteosarcoma.
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http://dx.doi.org/10.1038/s41598-017-05819-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511279PMC
July 2017

Treatment with Rhodiola crenulata root extract ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular fatty acid translocase/CD36 redistribution in skeletal muscle.

BMC Complement Altern Med 2016 Jul 12;16:209. Epub 2016 Jul 12.

The Laboratory of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China.

Background: Rhodiola species have been used for asthenia, depression, fatigue, poor work performance and cardiovascular diseases, all of which may be associated with insulin resistance. To disclose the underlying mechanisms of action, the effect of Rhodiola crenulata root (RCR) on insulin resistance was investigated.

Methods: Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. The indexes of lipid and glucose homeostasis were determined enzymatically and/or by ELISA. Gene expression was analyzed by Real-time PCR, Western blot and/or confocal immunofluorescence.

Results: RCR extract (50 mg/kg) suppressed fructose-induced hyperinsulinemia and the increases in the homeostasis model assessment of insulin resistance index and the adipose tissue insulin resistance index in rats. Additionally, this treatment had a trend to restore the ratios of glucose to insulin and non-esterified fatty acids (NEFA) to insulin. Mechanistically, RCR suppressed fructose-induced acceleration of the clearance of plasma NEFA during oral glucose tolerance test (OGTT), and decreased triglyceride content and Oil Red O staining area in the gastrocnemius. Furthermore, RCR restored fructose-induced sarcolemmal overexpression and intracellular less distribution of fatty acid translocase/CD36 that contributes to etiology of insulin resistance by facilitating fatty acid uptake.

Conclusion: These results suggest that RCR ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle. Our findings may provide a better understanding of the traditional use of Rhodila species.
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http://dx.doi.org/10.1186/s12906-016-1176-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942897PMC
July 2016

miR-21 synergizes with BMP9 in osteogenic differentiation by activating the BMP9/Smad signaling pathway in murine multilineage cells.

Int J Mol Med 2015 Dec 9;36(6):1497-506. Epub 2015 Oct 9.

Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.

Bone morphogenetic proteins (BMPs), particularly BMP9, have been shown to promote the osteogenic differentiation of murine multilineage cells (MMCs) and to promote bone formation in bone diseases; however, the mechanisms involved remain poorly understood. MicroRNAs (miRNAs or miRs) have been proven to regulate mesenchymal stem cell (MSC) differentiation. In this study, we identified a novel mechanism that unravels the functional axis of a key miRNA (miR-21) which contributes to BMP9‑induced osteogenic differentiation. We screened differentially expressed miRNAs in MMCs during BMP9‑induced osteogenic differentiation and found that miR-21 was significantly upregulated by BMP9 during the osteogenesis of MMCs. Furthermore, miR-21 was confirmed to promote the osteogenic differentiation of the MMCs by suppressing Smad7, which negatively regulates the osteogenic differentiation of MMCs. The upregulation of miR-21 may promote the osteogenic differentiation of MMCs in synergy with BMP9. The findings of our study revealed a novel function of miR-21, and suggest that the overexpression of miR-21 contributes to bone formation by promoting BMP9‑induced osteogenic differentiation. Our data may provide a molecular basis for the development of novel therapeutic strategies to treat bone diseases, such as osteoporosis and other inflammatory bone diseases.
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http://dx.doi.org/10.3892/ijmm.2015.2363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678163PMC
December 2015

NOV inhibits proliferation while promoting apoptosis and migration in osteosarcoma cell lines through p38/MAPK and JNK/MAPK pathways.

Oncol Rep 2015 Oct 24;34(4):2011-21. Epub 2015 Jul 24.

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.

The nephroblastoma overexpressed (NOV) gene, a member of the CCN gene family that encodes secreted proteins involved in a variety of processes including tumorigenesis, is often altered in a variety of tumors, including osteosarcoma. Recent studies indicated that NOV promotes osteosarcoma metastasis, but its biological functions and molecular mechanisms on osteosarcoma proliferation have yet to be fully elucidated. The aim of the present study was to examine the role of NOV in osteosarcoma biology. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were performed to characterize the endogenous expression of NOV in osteosarcoma cell lines. Recombinant adenovirus expressing NOV/siNOV (AdNOV/AdsiNOV) was used to infect osteosarcoma cell lines with a relatively low/high endogenous NOV expression to determine the functional relevance of NOV expression to osteosarcoma cell growth and migration in vitro, respectively. As a result, osteosarcoma cell proliferation was significantly reduced by NOV upregulation, indicated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltrazolium bromide (MTT), colony forming assay and cell cycle analysis. Cell apoptosis was markedly induced, as indicated by Hoechst 33258 staining assay and flow cytometry (FCM) detection. Despite the antiproliferative effect, NOV-transfected osteosarcoma cells exhibited increased migration ability. The possible molecular mechanisms underlying the biological role of NOV were also investigated. The results demonstrated that NOV increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) mitogen-actived protein kinases (MAPKs) in osteosarcoma cell lines. When the phosphorylation of p38 and JNK were inhibited by SB203580 (p38 inhibitor) or SP600125 (JNK inhibitor), respectively, the NOV-induced proliferation inhibition and cell apoptosis were reversed. In conclusion, the results revealed that NOV regulates the tumor growth of osteosarcoma cells through activation of the MAPK signaling pathway and promotes osteosarcoma cell migration in vitro.
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http://dx.doi.org/10.3892/or.2015.4153DOI Listing
October 2015

[Regulatory effect of ginsenoside Rh2 on HDAC1/2 activity and cyclin in human erythroleukemia K562 cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2014 Oct;30(10):1062-6

Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China.

Objective: To investigate the effects of the 20(S)-ginsenoside Rh2 [Rh2(S)]on cell proliferation, histone deacetylase 1 (HDAC1) and HDAC2 activity, and expression of cyclin in human erythroleukemia K562 cells.

Methods: The K562 cells were treated with Rh2(S) at various concentrations (10-80 μmol/L). Cell proliferation activity was detected by CCK-8 assay. Flow cytometry (FCM) was used to detect cell cycle and apoptotic changes. The HDAC activity of cells was measured by chemical colorimetry. The protein expressions of HDAC1, HDAC2, cyclin D1, CDK4, p16INK4A and p21 after 48 hour-treatment of Rh2 (S) (10, 20, 40, 60 μmol/L) were examined by Western blotting.

Results: The proliferation of K562 cells was inhibited by Rh2 (S) (20-80 μmol/L) in dose-and time-dependent manner. FCM analyses revealed that the number of the K562 cells treated with 60 μmol/L Rh2(S) was arrested in G0/G1 phase. The apoptosis rates of K562 cells were respectively (8.09±0.86)%, (9.44±0.53)% and (22.80±2.16)% after induced by 20, 40, 60 μmol/L Rh2(S), which showed statistically significant difference (P<0.05) compared with the control group (2.63±0.14)%. HDAC activity of the cells treated with Rh2(S) (40, 60 μmol/L) was reduced. Western blotting showed that the expressions of HDAC1, HDAC2, cyclin D1 and CDK4 decreased after induced by Rh2(S), and p16INK4A, p21 proteins were enhanced significantly.

Conclusion: The Rh2(S) can inhibit the proliferation of K562 cells and induce its cycle arrest and apoptosis through inhibiting HDAC1 and HDAC2 activity, down-regulating the expression of cyclin D1 and activating p16INK4A and p21.
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October 2014

[Inhibitory effect of trichostatin A on HepG2 cell proliferation and the mechanisms].

Nan Fang Yi Ke Da Xue Xue Bao 2014 Jun;34(7):917-22

Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. E-mail:

Objective: To investigate the inhibitory effect of trichostatin A (TSA) on the proliferation of HepG2 cells and explore the underlying mechanism.

Methods: HepG2 cells exposed to different concentrations of TSA for 24, 48, or 72 h were examined for cell growth inhibition using a cell counting kit, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining, and cell morphology changes under inverted microscope. The expressions of beta-catenin, HDAC1, HDAC3, H3K9, cyclinD1 and Bax proteins in the exposed cells were detected by Western blotting, and the expressions of HDAC1 and HDAC3 mRNAs by quantitative fluorescent PCR.

Results: Exposure to TSA caused significant dose- and time-dependent inhibition of HepG2 cell proliferation (P<0.05) and resulted in increased cell percentage in G0/G1 and G2/M phases and decreased cell percentage in S phase. The apoptotic index in the control group was (6.22 ± 0.25)%, which increased to (7.17 ± 0.20)% and (18.14 ± 0.42)% after exposure to 250 and 500 nmol/L TSA, respectively. Exposure to 250 and 500 nmol/L TSA also caused cell morphology changes with numerous floating cells. The expressions of beta-catenin, H3K9 and Bax proteins were significantly increased and CyclinD1, HDAC1, and HDAC3 protein expressions decreased in TSA-treated cells, but the expressions of HDAC1 and HDAC3 mRNAs showed no significant changes.

Conclusions: TSA can inhibit the proliferation of HepG2 cells and induce cell cycle arrest and apoptosis by inhibiting HDAC activity, promoting histone acetylation, and activating Wnt/beta-catenin signaling pathway.
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June 2014

Effect of ginsenoside Rh2 on the migratory ability of HepG2 liver carcinoma cells: recruiting histone deacetylase and inhibiting activator protein 1 transcription factors.

Mol Med Rep 2014 Oct 18;10(4):1779-85. Epub 2014 Jul 18.

Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 40016, P.R. China.

In previous experiments, ginsenoside Rh2 induced apoptosis and cell cycle arrest, which indicates a potential role for ginsenoside Rh2 in anticancer treatment. The effect of ginsenoside Rh2 on cancer is marked and ginsenoside Rh2 has been shown to inhibit pancreatic tumor migratory ability. In the present study, Transwell chambers were used in order to investigate whether ginsenoside Rh2 inhibits the migratory ability of HepG2 liver carcinoma cells. Furthermore, to analyze activator protein 1 (AP-1) transcription factor expression following Rh2 treatment, ten plasmids encoding Renilla luciferase coupled to the transcription factors were transiently transfected into the HepG2 cells and luciferase was detected by the Luciferase Reporter Assay system reagent. The results indicated that ginsenoside Rh2 inhibited HepG2 cell migratory ability. The expression levels of AP-1 transcription factors were increased in HepG2 cells following induction by phorbol 12-myristate 13-acetate, but ginsenoside Rh2 suppressed this induced AP‑1 expression. AP-1 transcription factors recruit histone deacetylase (HDAC)4 and affect its transcription, thus, the expression levels of HDAC4 were also analyzed, and these were found to be increased in the Rh2 treatment group. Matrix metalloproteinase 3 (MMP3), a gene downstream of AP-1, was then investigated, and the treatment group expressed reduced levels of MMP3 gene and protein. Therefore, the inhibitory effect of ginsenoside Rh2 on the migratory ability of HepG2 may be presumed to occur by the recruitment of HDAC and the resulting inhibition of AP‑1 transcription factors, in order to reduce the expression levels of MMP3 gene and protein.
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http://dx.doi.org/10.3892/mmr.2014.2392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148366PMC
October 2014

Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats.

BMC Complement Altern Med 2014 May 27;14:174. Epub 2014 May 27.

Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW 2000, Australia.

Background: The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys.

Methods: The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR.

Results: In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1.

Conclusions: The present results suggest that ginger supplement diminishes fructose-induced kidney injury through suppression of renal overexpression of macrophage-associated proinflammatory cytokines in rats. Our findings provide evidence supporting the protective effect of ginger on the metabolic syndrome-associated kidney injury.
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http://dx.doi.org/10.1186/1472-6882-14-174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047007PMC
May 2014

Matrix metalloproteinase 9 (MMP-9) in osteosarcoma: review and meta-analysis.

Clin Chim Acta 2014 Jun 1;433:225-31. Epub 2014 Apr 1.

College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry of Education, Chongqing Medical University, 400016, China. Electronic address:

The aim of this study is to determine the value of matrix metalloproteinase 9 (MMP-9) in diagnosis of osteosarcoma (OS). A systematic review and meta-analysis was conducted using MEDLINE, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, China Biomedical literature Database (CBM) and China National Knowledge Internet (CNKI) from inception through Aug 29, 2013. Articles written in English or Chinese that investigated the accuracy of MMP-9 for the diagnosis of OS were included. Pooled sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) were determined. I(2) was used to test heterogeneity and source of heterogeneity was investigated by meta-regression (tested with Meta-DiSc and STATA 12.0 statistical softwares). A total of 3729 articles were retrieved, of which 18 were included, accounting for 892 patients. Overall, the pooled sensitivity, specificity and AUC were 0.78 (95% CI 0.730-0.83), 0.90 (95% CI 0.79-0.95), and 0.87 (95% CI 0.83-0.89), respectively. The studies had substantial heterogeneity (I(2)=84%, 95% CI 65-100) (96%, 95% CI 94-99). Assay kit subgroup was the main source of the heterogeneity. Although MMP-9 was identified as a potential biomarker for OS, more studies were clearly needed to establish its diagnostic value.
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http://dx.doi.org/10.1016/j.cca.2014.03.023DOI Listing
June 2014

BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.

Mol Biol Rep 2014 Mar 12;41(3):1373-83. Epub 2014 Jan 12.

Department of General Surgery, The First Affiliated Hospitals of Chongqing Medical University, Chongqing, 400016, China.

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.
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http://dx.doi.org/10.1007/s11033-013-2982-8DOI Listing
March 2014

Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling.

Oncol Rep 2013 Oct 5;30(4):1723-30. Epub 2013 Aug 5.

Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.

Osteosarcoma (OS) is the most common type of bone cancer. Even with early diagnosis and aggressive treatment, the prognosis for OS is poor. In the present study, we investigated the proliferation and invasion inhibitory effect of dihydroartemisinin (DHA) on human OS cells and the possible molecular mechanisms involved. We demonstrated that DHA can inhibit proliferation, decrease migration, reduce invasion and induce apoptosis in human OS cells. Using an in vivo tumor animal model, we confirmed that DHA can prevent OS formation and maintain intact bone structure in athymic mice. In addition, we examined the possible molecular mechanisms mediating the function of DHA. We found that the total protein levels and transcriptional activity of β-catenin in OS cells are reduced by DHA treatment, and this may result from the increased catalytic activity of glycogen synthase kinase 3β (GSK3β). Moreover, the inhibitory effect of DHA on OS cells is reversed by overexpression of β-catenin, but is further enhanced by knockdown of β-catenin, respectively. Collectively, our results reveal that DHA can inhibit tumor growth of OS cells by inactivating Wnt/β-catenin signaling. Therefore, DHA is a promising chemotherapy agent in the treatment of human OS.
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http://dx.doi.org/10.3892/or.2013.2658DOI Listing
October 2013

Oleanolic Acid diminishes liquid fructose-induced Fatty liver in rats: role of modulation of hepatic sterol regulatory element-binding protein-1c-mediated expression of genes responsible for de novo Fatty Acid synthesis.

Evid Based Complement Alternat Med 2013 2;2013:534084. Epub 2013 May 2.

Faculty of Basic Medical Sciences, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China ; College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.

Oleanolic acid (OA), contained in more than 1620 plants and as an aglycone precursor for naturally occurred and synthesized triterpenoid saponins, is used in China for liver disorders in humans. However, the underlying liver-protecting mechanisms remain largely unknown. Here, we found that treatment of rats with OA (25 mg/kg/day, gavage, once daily) over 10 weeks diminished liquid fructose-induced excess hepatic triglyceride accumulation without effect on total energy intake. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in OA-treated rats. Hepatic gene expression profile demonstrated that OA suppressed fructose-stimulated overexpression of sterol regulatory element-binding protein-(SREBP-) 1/1c mRNA and nuclear protein. In accord, overexpression of SREBP-1c-responsive genes responsible for fatty acid synthesis was also downregulated. In contrast, overexpressed nuclear protein of carbohydrate response element-binding protein and its target genes liver pyruvate kinase and microsomal triglyceride transfer protein were not altered. Additionally, OA did not affect expression of peroxisome proliferator-activated receptor-gamma- and -alpha and their target genes. It is concluded that modulation of hepatic SREBP-1c-mediated expression of the genes responsible for de novo fatty acid synthesis plays a pivotal role in OA-elicited diminishment of fructose-induced fatty liver in rats.
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http://dx.doi.org/10.1155/2013/534084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659486PMC
July 2013

S100A8 and S100A9 are associated with colorectal carcinoma progression and contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.

PLoS One 2013 26;8(4):e62092. Epub 2013 Apr 26.

Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.

Background And Objective: S100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC) is associated with tumor size. Here, we investigated the clinical significances of S100A8 and S100A9 in tumor cells of CRC and their underlying molecular mechanisms.

Methods: Expression of S100A8 and S100A9 in colorectal carcinoma and matching distal normal tissues were measured by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. CRC cell lines treated with the recombinant S100A8 and S100A9 proteins were used to analyze the roles and molecular mechanisms of the two proteins in CRC in vitro.

Results: S100A8 and S100A9 were elevated in more than 50% of CRC tissues and their expression in tumor cells was associated with differentiation, Dukes stage and lymph node metastasis. The CRC cell lines treatment with recombinant S100A8 and S100A9 proteins promoted the viability and migration of CRC cells. Furthermore, the two recombinant proteins also resulted in the increased levels of β-catenin and its target genes c-myc and MMP7. β-catenin over-expression in CRC cells by Adβ-catenin increased cell viability and migration. β-catenin knock-down by Adsiβ-catenin reduced cell viability and migration. Furthermore, β-catenin knockdown also partially abolished the promotive effects of recombinant S100A8 and S100A9 proteins on the viability and migration of CRC cells.

Conclusions: Our work demonstrated that S100A8 and S100A9 are linked to the CRC progression, and one of the underlying molecular mechanisms is that extracellular S100A8 and S100A9 proteins contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062092PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637369PMC
November 2013

Improvement of liquid fructose-induced adipose tissue insulin resistance by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines.

Evid Based Complement Alternat Med 2013 21;2013:590376. Epub 2013 Feb 21.

Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.

Adipose tissue insulin resistance (Adipo-IR) results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of "lipotoxicity." Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities. Here we found that treatment with the alcoholic extract of ginger (50 mg/kg/day, by oral gavage) for five weeks attenuated liquid fructose-induced hyperinsulinemia and an increase in the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. More importantly, ginger reversed the increases in the Adipo-IR index and plasma nonesterified fatty acid concentrations during the oral glucose tolerance test assessment. Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers. Consistently, the macrophage-associated cytokines tissue necrosis factor alpha and interleukin-6 were also downregulated. In contrast, insulin receptor substrate (IRS)-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic protein (MCP)-1 and its receptor chemokine (C-C motif) receptor-2 were also suppressed. Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines.
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http://dx.doi.org/10.1155/2013/590376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594984PMC
March 2013

Treatment with ginger ameliorates fructose-induced Fatty liver and hypertriglyceridemia in rats: modulation of the hepatic carbohydrate response element-binding protein-mediated pathway.

Evid Based Complement Alternat Med 2012 6;2012:570948. Epub 2012 Nov 6.

Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.

Ginger has been demonstrated to improve lipid derangements. However, its underlying triglyceride-lowering mechanisms remain unclear. Fructose overconsumption is associated with increase in hepatic de novo lipogenesis, thereby resulting in lipid derangements. Here we found that coadministration of the alcoholic extract of ginger (50 mg/kg/day, oral gavage, once daily) over 5 weeks reversed liquid fructose-induced increase in plasma triglyceride and glucose concentrations and hepatic triglyceride content in rats. Plasma nonesterified fatty acid concentration was also decreased. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in ginger-treated rats. However, ginger treatment did not affect chow intake and body weight. Further, ginger treatment suppressed fructose-stimulated overexpression of carbohydrate response element-binding protein (ChREBP) at the mRNA and protein levels in the liver. Consequently, hepatic expression of the ChREBP-targeted lipogenic genes responsible for fatty acid biosynthesis was also downregulated. In contrast, expression of neither peroxisome proliferator-activated receptor- (PPAR-) alpha and its downstream genes, nor PPAR-gamma and sterol regulatory element-binding protein 1c was altered. Thus the present findings suggest that in rats, amelioration of fructose-induced fatty liver and hypertriglyceridemia by ginger treatment involves modulation of the hepatic ChREBP-mediated pathway.
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http://dx.doi.org/10.1155/2012/570948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502023PMC
November 2012

Abnormal expression of the mitotic checkpoint protein BubR1 contributes to the anti-microtubule drug resistance of esophageal squamous cell carcinoma cells.

Oncol Rep 2013 Jan 31;29(1):185-92. Epub 2012 Oct 31.

Key Laboratory of Diagnostic Medicine designated by The Chinese Ministry of Education and School of Diagnostic Medicine, Chongqing Medical University, Chongqing 400016, PR China.

Esophageal cancer is a common malignancy with a high mortality rate. The lack of effective chemotherapy and a means to overcome drug resistance leads to the predictable failure of esophageal cancer treatment. Mitotic checkpoint proteins play a critical role in regulating the cell cycle and proliferation. Abnormal expression of the mitotic checkpoint protein BubR1 has been reported in several types of cancers. In this study, we investigated the role of BubR1 in conferring resistance of esophageal cancer cells to anti-microtubule drugs. Using quantitative real-time PCR analysis on 50 samples of paired esophageal squamous cell cancer (ESC) tissues and adjacent non-cancerous tissues, we found that 72% (36 of 50) of the analyzed ESC samples exhibited high expression levels of BubR1, which was also confirmed in ESC cell lines. ESC cells with high levels of BubR1 were less sensitive to the anti-microtubule drugs paclitaxel and nocodazole. Recombinant adenovirus-mediated enforced expression of BubR1 in relatively sensitive ESC cell lines resulted in increased resistance to paclitaxel. Conversely, RNAi-mediated knockdown of BubR1 restored ESC cell sensitivity to paclitaxel. Cell cycle analysis indicated that the sub-G1 population increased in the ESC cells with reduced BubR1 levels. Taken together, our results suggest that upregulation of BubR1 expression may be associated with ESC resistance to paclitaxel treatment. Thus, BubR1 may serve as a potential chemosensitizing target to overcome chemoresistance.
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http://dx.doi.org/10.3892/or.2012.2117DOI Listing
January 2013

Defective osteogenic differentiation in the development of osteosarcoma.

Sarcoma 2011 22;2011:325238. Epub 2011 Feb 22.

Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL 60637, USA.

Osteosarcoma (OS) is associated with poor prognosis due to its high incidence of metastasis and chemoresistance. It often arises in areas of rapid bone growth in long bones during the adolescent growth spurt. Although certain genetic conditions and alterations increase the risk of developing OS, the molecular pathogenesis is poorly understood. Recently, defects in differentiation have been linked to cancers, as they are associated with high cell proliferation. Treatments overcoming these defects enable terminal differentiation and subsequent tumor inhibition. OS development may be associated with defects in osteogenic differentiation. While early regulators of osteogenesis are unable to bypass these defects, late osteogenic regulators, including Runx2 and Osterix, are able to overcome some of the defects and inhibit tumor propagation through promoting osteogenic differentiation. Further understanding of the relationship between defects in osteogenic differentiation and tumor development holds tremendous potential in treating OS.
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http://dx.doi.org/10.1155/2011/325238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061279PMC
July 2011

Total saponins of Panax ginseng induces K562 cell differentiation by promoting internalization of the erythropoietin receptor.

Am J Chin Med 2009 ;37(4):747-57

Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing 400016, China.

Ginseng is a commonly used herbal medicine with a wide range of therapeutic benefits. Total saponins of Panax ginseng (TSPG) is one of the main effective components of ginseng. Our previous studies have shown that TSPG could promote the production of normal blood cells and inhibition of the leukemia cell proliferation. However, whether ginseng can induce the differentiation of leukemia cells is still unclear. This study was to examine the effect of TSPG or the combination of erythropoietin (EPO) and TSPG on the erythroid differentiation of K562 cells, and their corresponding mechanisms regarding erythropoietin receptor (EPOR) expression. Under light and electron microscopes, the TSPG- or TSPG + EPO-treated K562 cells showed a tendency to undergo erythroid differentiation; early and intermediate erythroblast-like cells were observed. Hemoglobin and HIR2 expressions were significantly increased. As determined by Western blotting analysis, the EPOR protein level in the K562 cytoplasmic membrane was significantly decreased after TSPG treatment, while its cytoplasm level increased in a dose-dependent manner. However, the total cellular EPOR level was unchanged. These results indicate that TSPG-induced erythroid differentiation of K562 cells may be accompanied by the internalization of EPOR. Thus, our study suggests that treatment with a combination of TSPG and EPO may induce erythroid differentiation of K562 cells at least in part through induction of EPOR internalization.
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http://dx.doi.org/10.1142/S0192415X09007211DOI Listing
November 2009

Microarray expression profiling of Yersinia pestis in response to berberine.

Planta Med 2009 Mar 3;75(4):396-8. Epub 2008 Dec 3.

Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, PR China.

Coptis chinensis Franch. is a natural herb widely used in China for prevention and treatment of infectious diseases. Plague is a deadly disease caused by Yersinia pestis. Coptis chinensis Franch. is considered the therapeutic agent of choice against plague rather than conventional antibiotics because of its low cost and low toxicity. Berberine is the major constituent of a Coptis chinensis Franch. extract. In the present study, DNA microarray was used to investigate the transcription of Y. pestis in response to berberine. The minimal inhibition concentration (MIC) of berberine to Y. pestis was determined with the liquid dilution method. The gene expression profile of Y. pestis was performed by exposing Y. pestis to berberine at a concentration of 10 x MIC for 30 min. Total RNA was extracted and purified from Y. pestis, reverse-transcribed to cDNA, and then labeled with Cy-dye probes. The labeled probes were hybridized to the microarray. The results were obtained by a laser scanner and analyzed with SAM software. A total of 360 genes were differentially expressed in response to berberine: 333 genes were upregulated, and 27 were downregulated. The upregulation of genes that encode proteins involved in metabolism was a remarkable change. In addition to a number of genes of unknown encoding or unassigned functions, genes encoding cellular envelope and transport/binding functions represented the majority of the altered genes. A number of genes related to iron uptake were induced. This study revealed global transcriptional changes of Y. pestis in response to berberine, hence providing insights into the mechanisms of Coptis chinensis Franch. against Y. pestis.
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http://dx.doi.org/10.1055/s-0028-1088381DOI Listing
March 2009
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