PI3K／AKT信号通过介导β-catenin通路的活性影响胶质瘤细胞的生长  

Inactivation of PI3K/AKT signaling inhibits glioma cell growth through modulation of β -catenin - mediated transcription

作　　者：兰凤鸣[1] 岳晓[1] 韩磊[1] 史振东[1] 杨旸[1] 邹建[1] 张安玲[1] 王广秀[1] 贾志凡[1] 浦佩玉[1] 康春生[1] 

机构地区：[1]天津医科大学总医院神经外科、天津医科大学中枢神经创伤修复与再生教育部重点实验室暨天津市神经损伤变异与再生重点实验室 ,300052

出　　处：《中华神经外科杂志》2012年第3期275-278,共4页Chinese Journal of Neurosurgery

基　　金：基金项目：教育部新世纪优秀人才支持计划资助项目（NCET-07-061）;国家自然科学基金资助项目（30971136）;天津市科技计划项目资助项目（09JCZDJC17600）

摘　　要：目的探讨P13K／AKT信号阻断后抑制胶质瘤细胞株LN229生长的分子机制。方法将溶解于DMSO的P13K抑制剂LY294002加到LN229细胞中，并设立对照组。应用Westernblot检测P—AKT的表达，MTT、细胞周期实验评价LY294002处理后细胞生长情况的变化，Transewell实验检测胶质瘤细胞侵袭能力的改变。TOP—FOP实验检测Wnt通路的活性，Westernblot检测加入LY294002后Wnt通路中重要蛋白的表达。结果Westernblot显示LY294002处理组P—AKT表达与对照组和DMSO组比较明显降低。MTT和Transewell实验证实加入LY294002后细胞的增殖侵袭能力降低，细胞周期实验显示G0／G1期比值增大，S期缩短。TOP—FOP实验说明LY294002处理组Wnt通路的活性较其他两组显著下降，Westernblot证明LN229细胞LY294002处理组中GSK3β、p-β-catenin表达升高，c—Myc、CyclinDl等β—catenin下游基因表达降低。结论PDK抑制剂LY294002可通过影响Wnt／β-catenin通路的活性而降低胶质瘤细胞的恶性表型。Objective To investigate the mechanism of PI3K/AKT signaling inhibitor LY294002 decreasing cell proliferation and invasive ability, notheds The phosphatidylinositol 3＇ -kinase （PI3K） inhibitor LY294002 （Sigma） and DMSO were added into LN229 cells, respectively. Western blot was used to detect the expression of p - AKT to show the effect of LY294002. The biological behavior changes of LN229 cells were evaluated by MTT, FCM and Transwell assay. Western blot was also undertaken to analyze the expression of some functional proteins related to β - catenin/Wnt signaling. Results PI3K/AKT inhibitor LY294002 dramatically down regulated the expression of p - AKT in LN229 cells. Inhibition of PI3K/AKT signaling with LY294002 suppressed proliferation of LN229 cells determined by MTr assay compared with DMSO and control groups. LY294002 significantly decreased the S phase fraction to 5.5% from 17.8% and 17.3% in the parental and DMSO treated groups, respectively. Transwell assay demonstrated decreased invasion capability of LN229 cell lines based on LY294002. Initial studies revealed that increasing concentration of LY294002 resulted in decreased expression of β -catenin, p -GSK- 3β, c -Myc and Cyclin D1. Conclusion These results suggest that the PI3K/AKT signaling pathway regulates glioma cell proliferation,in part via repression of the Wnt/β -catenin pathway.

关 键 词：神经胶质瘤 PI3K抑制剂 LY294002 P-AKT β-catenin 

分 类 号：R739.41[医药卫生—肿瘤]