过表达NDRG1对TGF-β诱导肺癌A549细胞上皮-间质转化的逆转作用  

NDRG1 suppresses TGF-β-induced epithelial-mesenchymal transition in lung cancer A549 cells

作　　者：刘浩[1] 宋莹[1] 贺智敏[1] 

机构地区：[1]广州医科大学附属肿瘤医院肿瘤研究所,广州510095

出　　处：《中国医师杂志》2015年第5期710-713,718,共5页Journal of Chinese Physician

摘　　要：目的 探讨NDRG1对转化生长因子β（TGF-β）诱导的人肺癌A549细胞上皮-间质转化（EMT）的逆转作用及可能机制.方法 转染NDRG1过表达质粒至A549细胞,采用5 μg/L TGF-β1处理细胞,相差显微镜观察细胞形态学变化;Transwell侵袭实验检测A549细胞侵袭能力;Real-time RT-PCR、Western blot分别检测NDRGl mRNA、蛋白的表达,Western blot检测EMT相关标志物钙黏蛋白（E-cadherin）和波形蛋白（Vimentin）,以及EMT相关信号分子Snail、AKT、Smad的表达.结果 TGF-131可诱导A549细胞向间质样细胞表型转化,上调间质样标志物Vimentin表达和下调上皮样标志物E-cadherin表达,并增强细胞侵袭能力;过表达NDRG1可逆转TGF-131的上述作用;且过表达NDRG1能够抑制AKT的磷酸化,下调EMT转录因子Snail的表达.结论 NDRG1能够逆转TGF-B1对人肺癌A549细胞上皮一间质转化的诱导作用,并降低细胞的侵袭能力,其机制可能与NDRG1抑制AKT/Snail信号有关.Objective To explore the effect and molecular mechanism of N-myc downstream regulated gene 1 （NDRG1） on transforming growth factor-beta （TGF-β）-induced epithelial-mesenchymal transition （EMT） in human lung cancer cells.Methods Lung cancer A549 cells were transfected with NDRG1 overexpressed vector,and then treated with 5 μg/L TGF-β1.The abilities of invasion were detected by Transwell assay.The expressions of NDRG1 mRNA and protein were analyzed by teal-time reverse transcription polymerase chain reaction （RT-PCR） were examined with Western blot.The expressions of EMT-associated markers E-cadherin and Vimentin,and EMT-associated signaling molecules Snail,AKT and Smad were detected with Western blot.Results We found that TGF-β1 treatment could induce morphological alteration of A549 cells from epithelial morphology to mesenchymal morphology.TGF-β1 significantly increased the migration of A549 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More importantly,overexpression of NDRG1 significandy reversed the effects of TGF-β1 on A549 cells.Moreover,NDRG1 significandy decreased the levels of phospho-AKT,and suppressed the expression of EMT-related transcription factor Snail.Conclusions NDRG1 could reverse the effects of TGF-β1 on EMT in A549 cells,by which mechanism is related to reduction of the expressions of phospho-AKT and Snail.

关 键 词：胞间信号肽类和蛋白质类/药理学/代谢 转化生长因子β/副作用 肺肿瘤/药物疗法/病理学 细胞转化 肿瘤/药物作用 上皮细胞/药物作用/病理学 间质细胞/药物作用/病理学 

分 类 号：R734.2[医药卫生—肿瘤]