Rg3 inhibits gemcitabine-induced lung cancer cell invasiveness through ROS-dependent, NF-κB- and HIF-1α-mediated downregulation of PTX3.

Authors:
Dr. Sylvanus Kampo, Ph.D., M.med., CRA., RN.
Dr. Sylvanus Kampo, Ph.D., M.med., CRA., RN.
First Affiliated Hospital of Dalian Medical University.
Ph.D. Student
Anesthesiology
Dalian , Liaoning | China
Muhammad Khan
Muhammad Khan
Quaid-i-Azam University
Pakistan
Ji Wei Liu
Ji Wei Liu
College of Chemistry and Chemical Technology
China
Qiu Yan
Qiu Yan
Dalian Medical University
China

J Cell Physiol 2019 Jul 9;234(7):10680-10697. Epub 2019 Jan 9.

Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian, China.

PTX3, a member of the long pentraxin subfamily, associated with innate immunity is indispensable for resistance to some cancer. Gemcitabine, an analog of cytosine arabinoside, has shown restrained benefits because of profound chemoresistance. The PTX3 expression on GEM in human lung cancer cells have not yet been clarified; the present study aimed to show reactive oxygen species (ROS) mediatory PTX3 expression through distinct mechanisms. Whereas ginsenoside Rg3 is a herbal medicine with strong antitumor activity. Furthermore, we tested the hypothesis; Rg3 abrogates GEM-induced production of ROS-mediated activation of Akt and extracellular signal-regulated kinase (ERK) pathways and inhibits nuclear piling-up of nuclear factor kappa B (NF-κB) and HIF-1α. On the basis of time and dose-dependent manner, our data demonstrated that GEM-induced PTX3 expression was dependent on ROS generation as it was abrogated by pretreatment of lung cancer cells with the free radical scavenger N-acetyl-l-cysteine. Our data demonstrated that PTX3 upregulation by GEM correlated with the time-dependent escalation of NF-κB and HIF-1α in the nucleus resulted from phosphorylation-induced degradation of IκBα, whereas HIF-1α upregulation was NF-κB-dependent. Increase in ROS expression in lung cancer cells on GEM treatment preceded the nuclear accumulation of NF-κB and HIF-1α and suppression of ROS diminished these effects. ERK1/2 and Akt activation mediated the effect of ROS on NF-κB and HIF-1α and their pharmacological inhibition suppressed GEM-induced PTX3. Our study findings reinforced the role regarding PTX3 signaling in GEM-induced resistance and pointed toward an unintended and undesired effect of chemotherapy and to get an active regimen; the synergy was associated with NF-κB downregulation in lung cancer.

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July 2019
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References

(Supplied by CrossRef)
Nuclear factor-B: A holy grail in cancer prevention and therapy
Aggarwal et al.
Current Signal Transduction Therapy 2006
The long pentraxin PTX3: A biomarker spanning from cardiovascular disorders to cancer
Bonacina et al.
Journal of Molecular Biomarkers and Diagnosis 2013
Reactive oxygen species activate the HIF-1α promoter via a functional NFκB site
Bonello et al.
Arteriosclerosis, Thrombosis, and Vascular Biology 2007
Mesenchymal stromal cell-derived PTX3 promotes wound healing via fibrin remodeling
Cappuzzello et al.
Journal of Investigative Dermatology 2016

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