Akt激酶抑制剂MK-2206诱导U2OS人骨肉瘤细胞凋亡与自噬  

MK-2206,an inhibitor of Akt,induced cell apoptosis and autophagy in U2OS cells

作　　者：王雪莹[1] 李照梅 周运生[2] 郭文莉 王凤泽[1] 

机构地区：[1]泰山医学院生物科学学院,山东泰安271016 [2]泰安市中心医院放疗中心,山东泰安271000 [3]淄博市博山区疾病预防控制中心,山东淄博255200

出　　处：《中国病理生理杂志》2014年第9期1580-1583,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81272683);山东省自然科学基金资助项目(No.ZR2011HQ034)

摘　　要：目的:研究Akt抑制剂MK-2206对U2OS细胞凋亡和自噬的影响。方法:采用MTT法检测MK-2206对U2OS细胞活力的影响,DNA片段末端标记试剂盒检测细胞凋亡的变化,免疫印迹法检测细胞内蛋白的表达,用LC3-II的表达量用来确定细胞的自噬水平。结果:MK-2206剂量依赖性地降低了U2OS细胞的活力;MK-2206能够促进caspase-9、caspase-3和PARP的活化切割而诱导U2OS细胞发生凋亡;MK-2206给药后可促进细胞内LC3-II的表达,氯喹阻断自噬后明显增强了MK-2206对U2OS细胞活力的抑制作用。结论:Akt抑制剂MK-2206能够诱导U2OS细胞发生凋亡和自噬;抑制自噬可促进MK-2206对U2OS细胞的毒性。AIM： To observe the effect of MK-2206,an inhibitor of Akt,on the cell apoptosis and autophagy of U2 OS cells. METHODS： The cell viability was detected by MTT assay. The cell apoptosis was analyzed by TdT-mediated dUTP nick end labeling assay. The expression of LC3-II was examined by Western blotting. RESULTS： MK-2206 inhibited the cell viability in a dose-dependent manner. MK-2206 induced the cell apoptosis via activation of caspase-3,caspase-9 and PARP. MK-2206 treatment substantially induced the U2 OS cell autophagy by increasing in the levels of LC3-II. Blockage of autophagy using chloroquine magnified MK-2206-induced cell death in U2 OS cells. CONCLUSION： The Akt inhibitor MK-2206 induces cell apoptosis and autophagy. Blocking autophagy magnifies MK-2206-induced the inhibition of the viability in U2 OS cells.

关 键 词：MK-2206 细胞凋亡 细胞自噬 U2OS细胞 

分 类 号：R966[医药卫生—药理学]