Ginsenoside Rh2 Improves the Cisplatin Anti-tumor Effect in Lung Adenocarcinoma A549 Cells via Superoxide and PD-L1

Background: Ginsenoside Rh2 (Rh2) is a major biological component of ginseng that exerts antitumor activities in multiple cancers including Non-Small Cell Lung Cancers (NSCLCs). Rh2 also enhances the anti-tumor effects of various chemotherapy drugs including cisplatin at relatively low concentrations. Here, the mechanistic role of Rh2 in chemotherapy-treated NSCLCs will be investigated. Methods: In this study, FACS, western blot and siRNA addition were used to analyze the role of Rh2 in cisplatin- treated lung adenocarcinoma A549 and H1299 cells. Results: Subsequent observations indicated that Rh2 enhanced cisplatin-induced NSCLCs A549 and H1299 cells apoptosis. Cisplatin-induced productive autophagy was repressed by Rh2 in A549 cells. Rh2 also enhanced cisplatin cytotoxicity by elevating superoxide dismutase activity and repressing cisplatin-induced superoxide generation. Conversely, Rh2 was found to repress cisplatin-induced phosphorylation of epidermal growth factor receptor, phosphoinositide 3-kinase, protein kinase B, and autophagy. Cisplatin-induced Programmed Death- Ligand 1 (PD-L1) expression was repressed by Rh2 via the superoxide. Conclusion: These findings suggest that Rh2 enhanced the function of cisplatin by repressing superoxide generation, PD-L1 expression, and autophagy in lung adenocarcinoma cells.