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目的:探讨磷脂酰肌醇-3-激酶(PI3K)抑制剂LY294002对卵巢癌化疗效果的影响,方法:将LY294002单独或与顺铂、紫杉醇联合作用于卵巢癌A2780、SKOV3细胞,MTT法检测DDP、顺铂单独或联合LY294002处理后对A2780、SKOV3细胞的抑制率;采用流式细胞技术检测药物单独或联合作用对A2780和SKOV3细胞凋亡的影响;应用Western blot检测A2780和SKOV3细胞中AKT及磷酸化AKT(p-AKT)蛋白表达的变化。结果:联合应用LY294002能够显著提高DDP、paelitaxel对A2780和SKOV3细胞抑制率;LY294002与DDP、paclitaxel的协同治疗指数小于1,二者起协同治疗作用;联合LY294002能够增加A2780和SKOV3细胞的凋亡水平。LY294002干预组与对照组相比p-AKT蛋白的表达降低,差异有统计学意义(P<0.01)结论:LY294002能够有效提高卵巢癌A2780和SKOV3细胞对化疗药物DDP和paclitaxel的敏感性,抑制PI3K/AKT介导的信号传导通路,可明显提高卵巢癌细胞的化疗效果。
To investigate the effect of LY294002, a PI3K inhibitor, on the chemotherapeutic effect of ovarian cancer. Methods: LY294002 alone or combined with cisplatin and paclitaxel was applied to ovarian cancer A2780 and SKOV3 cells. MTT assay was used to detect the expression of DDP , Cisplatin alone or in combination with LY294002 treatment on A2780, SKOV3 cells inhibition; using flow cytometry alone or combined with drugs on apoptosis in A2780 and SKOV3 cells; Western blot was used to detect A2780 and SKOV3 cells AKT and Changes in phosphorylated AKT (p-AKT) protein expression. Results: The combination of LY294002 with DDP and paelitaxel significantly reduced the inhibition rate of A2780 and SKOV3 cells. The synergistic therapeutic index of LY294002 with DDP and paclitaxel was less than 1. The combination of LY294002 and LY294002 could increase the apoptosis of A2780 and SKOV3 cells . LY294002 intervention group compared with the control group p-AKT protein expression decreased, the difference was statistically significant (P <0.01) Conclusion: LY294002 can effectively improve the ovarian cancer A2780 and SKOV3 cells on the chemotherapeutic drugs DDP and paclitaxel sensitivity, inhibition of PI3K / AKT-mediated signal transduction pathway, can significantly improve the ovarian cancer cell chemotherapeutic effect.