PI3K/AKT特异性抑制剂LY294002对卯巢癌化疗增敏作用的研究  

Sensitization of Phosphatidylinositol 3'-Kinase-AKT Inhibitor LY294002 in Chemotherapy on Human Ovarian Cancer Cells

作　　者：吴卉娟[1] 王珂[1] 陈颖[1] 郝权[1] 刘文欣[1] 卢运萍[2] 马丁[2] 

机构地区：[1]天津市肿瘤防治重点实验室,天津医科大学附属肿瘤医院妇瘸科,天津市300060 [2]华中科技大学同济医学院妇产科

出　　处：《中国肿瘤临床》2010年第20期1141-1144,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30901742);国家973重点基础研究发展计划资助(编号:2009CB521800)~~

摘　　要：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。Objective： To explore the effect of PI3K/AKT inhibitor LY294002 on sensitization to chemotherapy （cisplatin and paclitaxel） on human ovarian cancer cell lines A2780 and SKOV3. Methods： Chemosensitivity of A2780 and SKOV3 cells to chemotherapy was measured using MTT assay when LY294002 was applied with cisplatin or paclitaxel individually or in combination. The apoptotic rates were detected by flow cytometry. The expression of AKT and p-AKT proteins was an- alyzed using Western blot. Results： Inhibition of A2780 and SKOV3 cell proliferation was increased significantly by cisplatin and paclitaxel in combination with LY294002 （P〈0.05）. LY294002 had synergistic effects with cisplatin and paclitaxel （com- bination index〈l）. The apoptotic index was increased by the joint application of the three drugs. Phosphorylated AKT pro- tein levels in A2780 and SKOV3 cells were clearly inhibited by LY294002, compared to the control group. There was a sta- tistical significance in the differences between the two groups （P〈0.01）. Conclusion： LY294002 can effectively enhance the sensitivity of A2780 and SKOV3 cells to cisplatin and paclitaxel. Inhibition of the PI3K/AKT signaling pathway can increase the chemotherapeutic effect of cisplatin and paclitaxel on human ovarian cancer cells.

关 键 词：LY294002 卵巢癌 PI3K/AKT 顺铂 紫杉醇 

分 类 号：R737.31[医药卫生—肿瘤]