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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 effect and significance of PI3K inhibitor LY294002 on the expression of AKT2 and MMP9 in human lung adenocarcinoma. Methods A549 lung adenocarcinoma cells were treated with LY294002 at different concentration (5μmol / L, 10μmol / L, 20μmol / L, 40μmol / L) for 24 hours. The protein expressions of AKT2 and MMP9 were detected by immunocytochemistry and Western blot respectively. Human lung adenocarcinoma A549 cells were inoculated subcutaneously in nude mice. The lung cancer xenograft model was established and treated with LY294002. The inhibition rate of LY294002 was calculated. The expression of AKT2 and MMP9 in xenografts of nude mice was detected by Western blot. Results The high expression of AKT2 and MMP9 in lung adenocarcinoma cell line A549 cells was detected. The expression of AKT2 and MMP9 protein was inhibited by P13K inhibitor LY294002, and the expression of AKT2 and MMP9 was decreased in a concentration - dependent manner. LY294002 can effectively inhibit the growth of xenografted tumor in nude mice, the inhibition rate was 40.30%. The levels of MMP9 and VKT2 in LY294002 group were significantly lower than those in control group (all P <0.01). Conclusions LY294002 can inhibit the activity of AKT2 and down-regulate the expression of MMP9 protein, which may be one of the mechanisms of anti-tumor growth and metastasis of PI3K inhibitor LY294002. PI3K may be the target of lung cancer treatment.