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.

Effects of lettuce glycoside B in ameliorating pulmonary fibrosis induced by irradiation exposure and its anti-oxidative stress mechanism.

The present research assessed the effects of lettuce glycoside B (LGB), a compound separated and purified from Pterocypsela laciniata, on irradiation-induced pulmonary fibrosis and explored the mechanism involved. Animal model of irradiation exposure inducing pulmonary fibrosis was established by Co irradiator. Rats were intraperitoneally treated with LGB (100, 200 and 400 mg/kg) once per day for a month. Lung index data were analyzed. The levels of fibrosis were assessed by hydroxyproline (Hyp) of pulmonary and lung tissue sections after irradiation exposure. Alveolitis and fibrosis levels were calculated from semi-quantitative analysis of hematoxylin and eosin and Masson's trichrome lung section staining. The serum levels of transforming growth factor ß1 (TGF-ß1), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) were also evaluated. Antioxidant enzymes of superoxide dismutase (SOD) were measured in serum. Moreover, we also measured serum malondialdehyde (MDA) levels, a marker of oxidative stress. Treatment with LGB significantly reduced mortality rates and lung index scores and MDA content, enhanced SOD and other antioxidant enzymes activity, and regulated serum levels of TGF-ß1, IL-6, and TNF-α. These results demonstrated that LGB significantly inhibited irradiation-induced pulmonary fibrosis. Furthermore, the results suggested promising clinical effect of LGB therapies for treating irradiation-induced pulmonary fibrosis.