Exogenous hydrogen sulfide promotes the proliferation, invasion and cisplatin resistance of human ovarian cancer cells through EGFR/PI3K/Akt signaling pathway / 上海交通大学学报（医学版）

ABSTRACT

Objective: To investigate the effects and mechanisms of exogenous hydrogen sulfide on the proliferation, apoptosis, invasion and cisplatin resistance of human ovarian cancer cells. Methods: The human ovarian cancer cell line SKOV3 cells and human cisplatin resistant cell line SKOV3/DDP cells were studied. The effects of NaHS on cell proliferation, apoptosis and invasion in SKOV3 cells were detected respectively by CCK-8, flow cytometry and Transwell invasion assay. The effect of NaHS on cisplatin resistance in SKOV3 and SKOV3/DDP cells was detected by calculating the IC50 and IR. The phosphorylation levels of EGFR, PI3K and Akt in SKOV3 and SKOV3/DDP cells were assayed by Western blotting. After treated with erlotinib (EGFR inhibitor), LY294002 (PI3K inhibitor) and MK-2206 (Akt inhibitor), the phosphorylation levels of EGFR, PI3K and Akt in SKOV3 and SKOV3/DDP cells, as well as cell proliferation, invasion in SKOV3 cells and cisplatin resistance in SKOV3/DDP cells were detected. Results: Compared with the control group, NaHS could significantly promote the proliferation (P=0.000) and invasion (P=0.033) in SKOV3 cells; increase IC50 (P=0.027, P=0.009) and decrease IR of cisplatin (P=0.001, P=0.009) in SKOV3 and SKOV3/DDP cells. NaHS could activate EGFR (P=0.000, P=0.037), PI3K (P=0.009, P=0.013) and Akt (P=0.000, P=0.023) in SKOV3 and SKOV3/DDP cells. Erlotinib, LY294002 and MK-2206 could block the effects of NaHS on the proliferation (all P=0.000) and invasion (all P<0.01) in SKOV3 cells, and also reverse the effect of NaHS on the cisplatin resistance in SKOV3/DDP cells (all P=0.000). Conclusion: Exogenous hydrogen sulfide can induce the proliferation and invasion in SKOV3 cells, and promote the cisplatin resistance in SKOV3 and SKOV3/DDP cells, which mechanisms are related to activation of EGFR/PI3K/Akt signaling pathway.