摘要
目的探讨PI3K抑制剂LY294002对肺腺癌AKT2及基质金属蛋白酶9(MMP9)表达的作用及意义。方法不同浓度(5μmol/L、10μmol/L、20μmol/L、40μmol/L)LY294002处理肺腺癌A549细胞24h后,分别用免疫细胞化学法和Western blot法检测AKT2、MMP9蛋白表达。人肺癌A549细胞接种于裸鼠皮下,建立肺癌裸鼠移植瘤模型并予LY294002治疗,计算LY294002的抑瘤率,Western blot法测定裸鼠移植瘤组织AKT2、MMP9蛋白的表达。结果肺腺癌细胞株A549细胞中存在AKT2、MMP9蛋白的高表达,应用P13K抑制剂LY294002可抑制该细胞株细胞中AKT2、MMP9蛋白的表达,而且其表达呈浓度依赖型降低。LY294002可有效抑制裸鼠移植瘤的生长,其抑瘤率为40.30%。LY294002治疗组裸鼠移植瘤组织MMP9及VKT2蛋白水平均显著低于对照组(P均<0.01)。结论 LY294002可抑制AKT2活性及下调MMP9蛋白的表达,该作用可能是PI3K抑制剂LY294002发挥抗肿瘤生长及及转移的机制之一。PI3K可能成为肺癌治疗的靶点。
Objective To investigate the function and significance of LY294002,a selective PI3K inhibitor,on AKT2 and matrix metalloproteinase-9（MMP9） expressions in human lung adenocarcinoma cancer.Methods A549 cells were treated with LY294002（5,10,20,40μmol/L） for 24h,the expressions of AKT2 and MMP9 were detected with immunohistochemistry and Western blot method.Human A549 lung cancer cells were inoculated subcutaneously in athymic nude mice to establish xenograft models.The mice were divided into LY294002 group and control group randomly.The inhibitory rate was calculated and expressions of AKT2 and MMP9 in xenografts were measured by Western blot.Results LY294002 inhibited the expression of AKT2,MMP9 in A549 cell in a dose-dependent manner.LY294002 inhibited the xenografts growth significantly and the inhibitory rate was 40.30%.Expressions of MMP9 and AKT2 were significantly reduced（P all0.01） in xenografts of LY294002 group compared with control group.Conclusions It is indicated that LY294002 can prevent the growth and invasion of tumors by inhibiting the expressions of AKT2 and MMP9,P13K may turn into the target in the treatment of lung cancer.
出处
《医药论坛杂志》
2011年第4期1-3,共3页
Journal of Medical Forum
