%0 Journal Article %T 外源性硫化氢通过 EGFR/PI3K/Akt 信号通路促进人卵巢癌细胞增殖、侵袭和顺铂耐药<br>Exogenous hydrogen sulfide promotes the proliferation, invasion and cisplatin resistance of human ovarian cancer cells through EGFR/PI3K/Akt signaling pathway %A 葛顺娜 %A 段峥峥< %A br> %A GE Shun-na %A DUAN Zheng-zheng %J 上海交通大学学报(医学版) %D 2018 %R 10.3969/j.issn.1674-8115.2018.03.00 %X 目的 · 探讨外源性硫化氢对人卵巢癌细胞增殖、凋亡、侵袭和顺铂耐药的作用及其机制。方法 · 以人卵巢癌细胞株 SKOV3 细胞和人顺铂耐药卵巢癌细胞株 SKOV3/DDP 细胞为研究对象。采用 CCK-8 法、流式细胞术、Transwell 侵袭小室实验,分别检测 NaHS 对 SKOV3 细胞的增殖、凋亡、侵袭能力的影响;通过计算细胞半数抑制浓度(half maximal inhibitory concentration,IC50)和 细胞活性抑制率(inhibition rate,IR),检测 NaHS 对 SKOV3 和 SKOV3/DDP 细胞顺铂耐药的影响;Western blotting 检测 NaHS 对 SKOV3 和 SKOV3/DDP 细胞中 EGFR、PI3K 和 Akt 磷酸化水平的影响;用 EGFR 的抑制剂 erlotinib、PI3K 的抑制剂 LY294002 和 Akt 的抑制剂 MK-2206 处理细胞,检测 SKOV3 和 SKOV3/DDP 细胞中 EGFR、PI3K 和 Akt 的磷酸化水平以及 SKOV3 细胞增殖、侵袭和 SKOV3/DDP 细胞顺铂耐药的变化。结果 · 与对照组相比,NaHS 能显著促进 SKOV3 细胞增殖(P=0.000)和侵袭(P=0.033);显著 提高 SKOV3 和 SKOV3/DDP 细胞对顺铂的 IC50 (P=0.027,P=0.009),降低顺铂对细胞的 IR(P=0.001,P=0.009);激活 SKOV3 和 SKOV3/DDP 细胞的 EGFR(P=0.000,P=0.037)、PI3K(P=0.009,P=0.013)、Akt(P=0.000,P=0.023);erlotinib、LY294002 和 MK- 2206 均能阻断 NaHS 对 SKOV3 细胞的增殖(均 P=0.000)和侵袭(均 P<0.01)作用,也能逆转 NaHS 促进 SKOV3/DDP 细胞对顺铂 耐药的作用(均 P=0.000)。结论 · 外源性硫化氢可促进 SKOV3 细胞的增殖和侵袭,以及 SKOV3 和 SKOV3/DDP 细胞的顺铂耐药, 其机制与激活 EGFR/PI3K/Akt 信号通路有关。<br>: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 %K < %K br /> %K 硫化氢 %K 卵巢癌 %K 细胞增殖 %K 细胞侵袭 %K 顺铂耐药 %K EGFR/PI3K/Akt 信号通路 %K < %K br> %K ?hydrogen sulfide %K ovarian cancer %K cell proliferation %K cell invasion %K cisplatin resistance %K EGFR/PI3K/Akt signaling pathway %U http://xuebao.shsmu.edu.cn/CN/abstract/abstract11832.shtml