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.