基于AKT/mT0RC1和HIF1/VEGF通路研究eIF4E基因调控肺腺癌血管新生中的作用机制  

Study on the mechanism of eIF4E regulation in lung angiogenesis adenocarcinoma based on AKT/mT0RC1 pathway and HIF1/VEGF pathway

作　　者：胡权腾 郭海谢[1] 吴春雷[1] 马德华[1] HU Quan-teng;GUO Hai-xie;WU Chun-lei;MA De-hua(Department of Thoracic Surgery,Taizhou Hospital,Taizhou,Zhejiang 317000,China)

机构地区：[1]浙江省台州医院胸外科,浙江台州317000

出　　处：《中国卫生检验杂志》2020年第18期2183-2185,2207,共4页Chinese Journal of Health Laboratory Technology

基　　金：浙江省医药卫生科技计划项目(2014KYB310)。

摘　　要：目的基于AKT/m T0RC1和HIF1/VEGF通路,研究e IF4E基因在肺腺癌血管新生中的作用及相关机制。方法本文选用RNAi技术沉默e IF4E基因,通过转染A549人肺癌细胞株,建立e IF4E基因低表达的肺腺癌细胞模型。免疫印迹检测e IF4E基因低表达后介导血管新生的AKT/m TORC1通路和HIF1/VEGF通路主要成员蛋白水平的变化。结果e IF4E在A549细胞中高表达,A549对照组与si-e IF4E组蛋白表达分别为(0.77±0.06)与(0.18±0.04),差异有统计学意义(P<0.05);si-e IF4E后,2组AKT蛋白表达差异无统计学意义(P>0.05),si-e IF4E组p-AKT蛋白表达明显低于A549对照组,差异有统计学意义(P<0.05);2组m TOR表达差异无统计学意义(P>0.05),si-e IF4E组m TORC1蛋白表达低于A549对照组,差异有统计学意义(P<0.05);si-e IF4E后,si-e IF4E组HIF1蛋白与VEGF蛋白表达明显低于A549对照组,差异有统计学意义(P<0.05)。结论抑制e IF4E基因可抑制肺腺癌细胞血管新生过程中AKT过度磷酸化,降低m TORC1表达,减少HIF1与VEGF生成。e IF4E基因可能是通过AKT/m TORC1通路和HIF1/VEGF通路参与肺腺癌血管新生过程。Objective To study the role of e IF4 E in angiogenesis of lung adenocarcinoma and its related mechanisms based on AKT/m T0 RC1 pathway and HIF1/VEGF pathway.Methods The e IF4 E was silenced by RNAi technology.The lung cancer cell with low expression of e IF4 E was established by transfecting A549 human lung cancer cell.Western blotting was used to detect the major member of protein levels after siRNA e IF4 E gene in AKT/m TORC1 pathway and the HIF1/VEGF pathway.Results EIF4 E was highly expressed in A549 cells,and the protein expression levels of A549 control group and si-EIF4 E histone group were(0.77±0.06)and(0.18±0.04),respectively,with the differences statistically significant(P<0.05).The difference of si-e IF4 E,AKT protein expression had no statistical significance between the two groups(P>0.05).The p-AKT protein expression in the Si-EIF4 E group was significantly lower than that in the A549 control group,and the differences were statistically significant(P<0.05),but not statistically significant on the difference on m TOR expression(P>0.05),m TORC1 protein expression in si-e IF4 E is lower than the A549 controls,with the differences statistically significant(P<0.05);after SI-EIF4 E,HIF1 and VEGF expressions in the Si-eif4 E group were significantly lower than those in the A549 control group,and the differences were statistically significant(P<0.05).Conclusion Inhibition of e IF4 E gene can inhibit the over-phosphorylation of AKT during angiogenesis of lung adenocarcinoma cells,reduce the expression of m TORC1,and reduce the generation of HIF1 and VEGF.EIF4 E gene may be involved in the angiogenesis process of lung adenocarcinoma through AKT/m TORC1 pathway and HIF1/VEGF pathway.

关 键 词：真核翻译起始因子4E 肺腺癌 血管新生 蛋白激酶B哺乳动物雷帕霉素蛋白敏感型复合体 缺氧诱导因子1/血管内皮生长因子 

分 类 号：R734.2[医药卫生—肿瘤]