下调线粒体转录因子A对肺腺癌细胞A549成瘤能力和药物敏感性的影响  

Down-regulation of Mitochondrial Transcription Factor A Inhibits Tumorigenesis and Enhances Chemosensitivity of Lung Adenocarcinoma A549 Cells

作　　者：伍潇怡 卢圆圆[1] 胡轲轲 蓝林华[1] 谢德耀[2] 刘永章[1] 吕斌[1] 

机构地区：[1]温州医科大学检验医学院生命科学学院浙江省医学遗传学重点实验室,温州325035 [2]温州医科大学附属第一医院心胸外科,温州325000

出　　处：《中国细胞生物学学报》2016年第4期375-381,共7页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:31070710;31171345;31570772)资助的课题~~

摘　　要：该文初步探讨了下调线粒体转录因子A(mitochondrial transcription factor A,TFAM)对人肺腺癌细胞A549的影响。该研究将靶向TFAM基因的sh RNA慢病毒载体感染A549细胞,应用蛋白免疫印迹(Western blot)方法检测TFAM蛋白质水平,划痕愈合实验检测细胞迁移能力,裸鼠成瘤实验检测细胞体内增殖能力,CCK-8实验和Western blot检测细胞毒性及细胞对药物敏感性。结果显示,该研究成功地在A549细胞中下调了TFAM蛋白质水平,TFAM敲低的细胞形态发生改变,愈合能力明显减弱,裸鼠成瘤能力减弱,裸鼠成瘤的体积和体重均具有显著差异,细胞毒性增强,且细胞对阿霉素的敏感性增强。结果表明,下调TFAM可影响细胞迁移能力和体内增殖能力,通过增加细胞凋亡提高肿瘤细胞对抗肿瘤药物阿霉素的敏感性,提示TFAM可作为肺腺癌治疗的潜在靶点。The aim of this study was to investigate the effect of down-regulation of mitochondrial transcription factor A（TFAM） on lung adenocarcinoma cell line A549. A549 cells were infected with control or TFAM-sh RNA lentiviral particles and the down-regulation of TFAM was confirmed by Western blot. Wound healing assay, nude mice tumorigenesis test, CCK-8 assay were carried out to examine the ability of cell migration, tumorigenesis in nude mice and cell viability of A549 cells, respectively. Our results showed that TFAM protein was significantly reduced by TFAM-sh RNA plasmids. Compared with the control group, TFAM depletion cells showed a morphology change and a significant decrease in migration ability. In addition, down-regulation of TFAM led to decreased tumorigenesis of A549 cell in nude mice. Furthermore, down-regulation of TFAM enhanced cell cytotoxicity and apoptosis after treating A549 cells with a gradient doxorubicin. Taken together, our findings demonstrated that down-regulation of TFAM inhibited tumorigenesis and enhanced chemosensitivity of A549 cells, indicating that TFAM might serve as a potential target in the treatment of human lung adenocarcinoma.

关 键 词：线粒体转录因子A A549细胞 细胞迁移 肿瘤形成 药物敏感性 

分 类 号：R734.2[医药卫生—肿瘤]