LY294002对LK2和H460肺肿瘤细胞系细胞增殖及SKP2和p27表达的影响  

Effect of PI3K inhibitor LY294002 on proliferation and expressions of SKP2 and p27 in lung cancer cell lines LK2,H460

作　　者：解智慧[1] 孙秀华[1] 柯丹[1] 张洪开[1] 于爱鸣[1] 

机构地区：[1]中国医科大学生物化学与分子生物学教研室,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2010年第3期182-185,205,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：辽宁省教育厅课题资助(2004D225)

摘　　要：目的:探讨PI3K抑制剂LY294002对肺肿瘤细胞增殖影响及其分子机制。方法:培养肺癌细胞系LK2和H460,LY294002阻断PI3K信号通路后,MTT比色法测定细胞生长曲线;FCM分析细胞周期变化;实时RT-PCR、蛋白印迹法分别观察PI3K信号下游蛋白SKP2、p27mRNA及蛋白表达变化。结果:与对照组相比,处理组细胞生长速率受抑制,细胞周期阻滞于G1期。实时RT-PCR及蛋白印迹结果显示,LY294002处理后SKP2mRNA、蛋白表达水平均降低,2种细胞中基因降低量分别为42%和41%,蛋白降低量为65%和55%,p27mRNA表达水平增加了49%和36%,但蛋白表达水平不变。结论:肺肿瘤细胞LK2和H460中PI3K通路通过SKP2,但并不经由p27调节细胞周期,调控细胞增殖。OBJECTIVE：To investigate the influence of PI3K inhibitor LY294002 on proliferation of lung cancer cells LK2,H460 and reveal the potential PI3K-dependent mechanism.METHODS：The influence of PI3K inhibitor LY294002 on proliferation of lung cancer cells LK2,H460 was investigated and the PI3K-independent mechanism was studied.RESULTS：Compared with the control group,the cellular growth of the LY294002-treated cells was inhibited and the cell cycles were arrested at G1 phase.Real-time RT-PCR and Western blot results revealed that the inhibition of PI3K signaling reduced the expression of SKP2 at both mRNA levels by 42% and 41% and protein levels by 65% and 55%,increased the expression of p27 mRNA by 49% and 36% respectively,while showed no alternations of p27 protein.CONCLUSION：These data implicate that PI3K signaling regulates the cell cycle and proliferation of lung cancer cells LK2,H460 through modulating SKP2 expression,while not via p27.

关 键 词：肺肿瘤 细胞系 肿瘤 细胞增殖 

分 类 号：R734.2[医药卫生—肿瘤]