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）

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.

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）

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.

Effects of genistein on apoptosis and EGFR/PI3K/Akt signal transductionpathway in triple-negative breast cancer MDA-MB-231 cells / 中国药理学通报

Aim To investigate the effect of genistein on apoptosis in triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms.Methods MTT assay was used to detect the inhibition rate on breast cancer MDA-MB-231 cells of genistein.Hoechst 33258 staining was applied to determine the effect of genistein on morphology of MDA-MB-231 cells.qRT-PCR was employed to detect the mRNA expression of EGFR in MDA-MB-231 cells.Western blot was utilized to determine the expression of Bcl-2, Bax, caspase-3, EGFR, Akt, and p-Akt.The expressions of Akt and p-Akt proteins in breast cancer MDA-MB-231 cells were detected after treated with Akt activator insulin, genistein and in combination with insulin.Results Genistein inhibited the viability of breast cancer MDA-MB-231 cells in a time-dependent manner.The results of Hoechst 33258 staining showed a typical apoptotic morphological changes of MDA-MB-231 cells after treatment of genistein for 36 h.qRT-PCR showed that the mRNA expression of EGFR in MDA-MB-231 cells decreased after treated with genistein for 36 h.The expression levels of Bcl-2, EGFR, Akt, p-Akt, ERK, p-ERK were significantly down-regulated(P<0.01) compared with control.While, the expression of Bax, caspase-3 was significantly up-regulated (P<0.01).It was observed that p-Akt was significantly activated after the treatment of Akt activator insulin (P<0.01), however, significantly down-regulated (P<0.01) when treated with genistein.Conclusion Genistein could inhibit the growth of triple-negative breast cancer MDA-MB-231 cells and induce apoptosis, which probably involves regulating EGFR/PI3K/Akt signaling pathway.