Mir-7上调增强肺腺癌对吉非替尼敏感性的机制研究

目的:探索上调Mir-7的表达使肺腺癌A549细胞增强吉非替尼的敏感性及其机制。方法:用lipo-fectamine2000携带Mir-7对A549细胞进行瞬时转染。将A549细胞分为对照组、转染组、吉非替尼组与联合组。MTT法测各组细胞增殖率变化,Transwell检测细胞侵袭性,Real time PCR检测E-Cadherin及N-Cad-herin的mRNA表达的变化,Western blot检测他们的蛋白表达的变化。结果:上调A549细胞中Mir-7的表达与吉非替尼共同作用较单独吉非替尼作用有更显著的抑制作用。用Mir-7转染后,肺腺癌A549细胞的侵袭力下降。转染与吉非替尼联合组E-Cadherin的信使RNA及蛋白的表达变化不大,但N-Cadherin表达下降。结论:上调Mir-7的表达可以增强肺腺癌细胞对吉非替尼的敏感性,其机制可能是过量表达的Mir-7抑制了IGF-1R信号通路及肿瘤上皮细胞间质化。

Mechanism of Mir- 7 enhancing sensitivity to Gefitinib in lung adenocarcinomas

Objective :To investigate if the cell’s sensitivity to Gefitinib can be enhanced by up-regulated Mir-7’s expression level and its mechanism in the human lung adenocarcinoma cell(A549 cell).Methods: The A549 cells were transfected by using lipofectamine2000 carry with the Mir-7 to and acted to Gefitinib.A549 cells were devided into 4 groups: transfection,Gefitinib,union and control.The proliferation of the cells was detected by 4-methyl-tetrazolium(MTT).E-Cadherin and N-Cadherin’s mRNA was detected by Real time PCR.Their protein’s expression was detected by Western blot.Results: The up-regulated Mir-7’s expression level of A549 cell with Gefitinib had more noticeable inhibition effect than Gefitinib alone.The cell’s invasiveness was decreased after Mir-7 transfection.There were no changes of expression E-Cadherin’s message RNA and protein in the transfection group and union group but the N-Cadherin’s decreased obviously.Conclusion: Mir-7 can enhance the cell’s sensitivity to Gefitinib.The mechanism of this phenomenon was the over-expressed Mir-7 can inhibit the epithelial-to-mesenchymal transition(EMT).