Publications by authors named "Maoli Liang"

5 Publications

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Quercetin induces pro-apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro.

Thorac Cancer 2021 Mar 11. Epub 2021 Mar 11.

Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, Tianjin, China.

Background: Quercetin, a natural flavonoid compound, is a potent cancer therapeutic agent widely found in fruit and vegetables. It has been reported to induce growth inhibition and apoptosis in both A549 and H1299 human lung cancer cells. However, the effect of quercetin-induced autophagy on apoptosis and the possible autophagy mechanism in A549 and H1299 cells have not yet been critically examined.

Methods: A549 and H1299 cells were treated with different concentrations of quercetin for 24 hours. Cell growth was measured by cell counting kit-8 (CCK-8) assay, whereas apoptosis was assessed by western blotting analysis of apoptotic proteins. The levels of proteins and genes involved in autophagy were determined by western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Autophagosomes were also observed by transmission electron microscopy (TEM) and LC3 immunofluorescence.

Results: Quercetin inhibited cell viability and induced mitochondria-dependent apoptosis in both A549 and H1299 cells in a dose-dependent. Moreover, quercetin also promoted the expression of LC3-II and beclin 1 and suppressed the expression of p62. The mRNA levels of LC3-II, beclin 1, Atg5, Atg7, and Atg12 were upregulated by quercetin treatment. Autophagy inhibition with 3-methyladenine could effectively inhibit quercetin-induced apoptosis. In addition, quercetin dose-dependently elevated the levels of SIRT1 protein and the pAMPK-AMPK ratio. Quercetin-induced autophagy was attenuated by SIRT1 inhibitor EX527 and SirT1 knockdown by small interfering RNA (siRNA).

Conclusions: Quercetin-induced autophagy contributes to apoptosis in A549 and H1299 lung cancer cells, which involved the SIRT1/AMPK signaling pathway.
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http://dx.doi.org/10.1111/1759-7714.13925DOI Listing
March 2021

Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy.

Thorac Cancer 2021 Mar 3. Epub 2021 Mar 3.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Background: Emerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non-small-cell lung cancer (NSCLC) remains unclear.

Methods: Cell counting kit-8 (CCK-8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells.

Results: Curcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin-1 (Fer-1) or knockdown of iron-responsive element-binding protein 2 (IREB2) notably weakened curcumin-induced anti-tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin-induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1.

Conclusion: Curcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13904DOI Listing
March 2021

Influence of coexistence of mild OSA on airway mucus hypersecretion in patients with COPD.

J Breath Res 2020 Dec 18. Epub 2020 Dec 18.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, CHINA.

Purpose: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) can cause multiple system damage, and the main physiological mechanisms are continuous hypoxia and intermittent hypoxia (IH). Airway mucus hypersecretion is an important clinical feature of COPD, which can cause a progressive decline of lung function, acute COPD aggravation, and disease progression. The purpose of our study is to determine the influence of the coexistence of mild OSA on airway mucus hypersecretion.

Patients And Methods: Clinical data and airway epithelial samples were collected. The average fluorescence intensity of MUC5AC and the number of goblet cells were measured through immunofluorescence staining. MUC5AC expression was measured in human bronchial epithelial (HBE) cells exposed to normoxia, IH, particulate matter (PM), and PM+IH using real-time quantitative polymerase chain reaction and western blotting.

Results: FEV1% pred and FEV1/FVC were higher in patients with COPD-OSA overlap syndrome(OS) than in patients with COPD alone. Patients with OS had less sputum volume than patients with COPD alone.MUC5AC expression and the number of goblet cells in the airway epithelium in the COPD alone group were significantly higher than those in the OS groups. The PM+IH group had lower MUC5AC mRNA and protein expression in HBE cells than the PM group.

Conclusions: The coexistence of mild OSA may reduce goblet cell proliferation and MUC5AC expression in the airway epithelium of patients with COPD. Mild IH inhibited PM-induced up-regulation of MUC5AC expression in the mRNA and protein levels in HBE cells.
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http://dx.doi.org/10.1088/1752-7163/abd52eDOI Listing
December 2020

Downregulation of m A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.

Thorac Cancer 2020 11 21;11(11):3269-3279. Epub 2020 Sep 21.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Background: m A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m A reader, is associated with multiple cancers; however, little is known of its role in non-small cell lung cancer (NSCLC).

Methods: The GEPIA, Oncomine and GEO databases were analyzed to assess expression of YTHDC2 in NSCLC patients. Quantitative polymerase chain reaction, western blot and immunohistochemistry were used to detect YTHDC2 expression in different NSCLC cell lines (H1299, H460, H292 and A549) and patients. The effects of YTHDC2 on NSCLC cell lines (A549 and H1299) proliferation and migration were employed using CCK8 and transwell assays. The potential target RNAs of YTHDC2 were obtained from the POSTAR database. Functional enrichment analysis of YTHDC2 targeted RNAs was performed using the Metascape database.

Results: GEPIA, Oncomine and GEO databases showed low expression of YTHDC2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. YTHDC2 expression was significantly decreased in different NSCLC cell lines and our clinical samples. Moreover, low expression of YTHDC2 was significantly associated with poor differentiation, lymph node metastasis, tumor size and stage. In addition, YTHDC2 could suppress the proliferation and migration ability of A549 and H1299 cell lines. Kaplan-Meier Plotter database analysis revealed that patients with low level of YTHDC2 had a significantly poor prognosis. Finally, functional enrichment analysis of YTHDC2 targeted RNAs indicated several enriched pathways related to cancer.

Conclusions: These findings elucidate that YTHDC2 suppresses tumorigenesis in NSCLC, indicating that YTHDC2 may be a promising therapeutic target for NSCLC.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: This study demonstrated that the downregulation of YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer (NSCLC).

What This Study Adds: YTHDC2 might be a promising therapeutic target for non-small cell lung cancer (NSCLC).
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http://dx.doi.org/10.1111/1759-7714.13667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606000PMC
November 2020

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea.

Respir Res 2018 02 12;19(1):28. Epub 2018 Feb 12.

Respiratory Department, Tianjin Medical University General Hospital, Tianjin, China.

Background: Recently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated.

Methods: C57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment. Then, the animals were randomly distributed into three groups (n = 8 each): normoxia (N) group, IH group, and antioxidant tempol group (IHT, exposed to IH after treatment with tempol). After the mice were sacrificed, the number and weight of lung metastatic colonies were assessed. The lung tissues with tumor metastasis were analyzed for markers of oxidative stress and inflammation and for HIF-1α using western blotting and real-time PCR (qRT-PCR). The level of reactive oxygen species (ROS) in B16F10 cell was also assessed after N, IH and IH with tempol treatments.

Results: Compared with normoxia, IH significantly increased the number and weight of mouse lung metastatic colonies. Treatment of B16F10 cells with IH significantly enhanced ROS generation. Lung tissues with tumor metastasis provided evidence of increased oxidative stress, as assessed by p22 and SOD mRNA levels and the NRF2 protein level, as well as increased inflammation, as assessed by TNF-α and IL-6 mRNA levels and the NF-κB P65 protein level. HIF-1α protein levels were increased in response to IH treatment. Tempol, an important antioxidant, ameliorated IH-induced melanoma lung metastasis in mice and reduced oxidative stress and inflammation responses.

Conclusions: These results support the hypothesis that oxidative stress and inflammation responses play an important role in the pathogenesis of OSA-like IH-induced melanoma lung metastasis in mice. Antioxidant intervention provides a novel strategy for the prevention and treatment of cancer in OSA populations.
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http://dx.doi.org/10.1186/s12931-018-0727-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809953PMC
February 2018