PI3K/Akt抑制剂对肺癌裸鼠移植瘤MMP9、VEGF表达的影响

Influence of PI3K inhibitor on expressions of MMP9 and VEGF in human lung cancer xenograft in nude mice

目的探讨PI3K抑制剂LY294002对肺癌裸鼠移植瘤的基质金属蛋白酶9(MMP9)及血管内皮生长因子(VEGF)表达的影响及意义。方法人肺癌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 b lot法测定裸鼠移植瘤组织MMP9、VEGF蛋白的表达。结果 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VEGF蛋白水平均显著低于对照组(P均<0.01)。结论 PI3K抑制剂LY294002通过下调MMP9及VEGF蛋白的表达,从而抑制肿瘤的侵润转移。

Objective To investigate LY294002,a selective PI3K inhibitor,on matrix metalloproteinase-9（MMP9） and vascular endothelial growth factor（VEGF） expressions human lung cancer xenografts in nude mice.Methods 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 MMP9 and VEGF in xenografts were measured by western blot.Results LY294002 inhibited the xenografts growth significantly and the inhibitory rate was 40.30%.Expressions of MMP9 and VEGF were significantly reduced（P〈0.01） in xenografts of LY294002 group compared with that of control group.Conclusions It is indicated that LY294002 can prevent the invasion and metastasis of tumors by inhibiting the expressions of MMP9 and VEGF in mouse esophageal cancer tissue clinically.