腺病毒介导的ING4基因抑制胃癌细胞生长及其分子机制  

Adenovirus-mediated ING4 gene suppresses gastric carcinoma cell growth and its molecular mechanism

作　　者：陆向东[1] 杨吉成[2] 谭洁[1] 程晓赪 周俊东[1] 李汉冲[1] 

机构地区：[1]南京医科大学附属苏州医院血液肿瘤科,江苏苏州215001 [2]苏州大学医学院细胞与分子生物学教研室,江苏苏州215123

出　　处：《南京医科大学学报（自然科学版）》2008年第10期1221-1228,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：南京医科大学自然科学基金(NY07013);苏州市自然科学基金(SZD0784)资助项目

摘　　要：目的:研究肿瘤生长抑制基因4(inhibitor of growth family4,ING4)体外对胃癌细胞SGC-7901的生长抑制及其分子机制。方法:将携带有人ING4基因的重组复制缺陷型腺病毒(Ad-hING4)感染胃癌细胞SGC-7901,RT-PCR法检测腺病毒介导的外源性hING4基因的转录,MTT法检测hING4基因对SGC-7901细胞的生长抑制作用,激光扫描共聚焦显微镜(LSCM)观察hING4基因诱导SGC-7901细胞凋亡的形态学改变,流式细胞仪(FACS)检测hING-4基因诱导胃癌细胞SGC-7901的凋亡率及细胞周期改变,免疫细胞化学分析凋亡相关因子bcl-2和bax的改变。结果:Ad-hING4感染SGC-7901细胞后,RT-PCR结果提示有hING4目的基因的转录,该基因表达可以显著抑制SGC-7901细胞的生长,诱导S期减少、G2/M期阻滞和凋亡,hING4基因能使SGC-7901细胞中bcl-2的表达下调和bax的表达上调。结论:重组腺病毒Ad-hING4对胃癌细胞SGC-7901具有显著的生长抑制及凋亡诱导作用,其作用机制可能与下调bcl-2基因和上调bax基因的表达有关。Objective：To study the growth inhibition effect and its molecular mechanism of SGC-7901 cells by the tumor suppressor gene hlNG4 in vitro. Methods：The hlNG4 gene was transfected into human gastric carcinoma cell line SGC-7901 with a replication-incompetent adenovims vector. The mRNA transcriptions of hlNG4 in SGC-7901 cells was confirmed using RT-PCR. The antitumor emcacy of hlNG4 on SGC-7901 cells was evaluated by MTT,and cell apoptosis were detected by Hoechest 33258 staining and laser scanning confocal microscopy （LSCM）. The cell cycle and distribution and apoptotic peak was evaluated by flow cytometry. Bcl-2 and Bax were explored by means of immunocytochemistry. Results：hING4 was proved successful transcription in SGC-7901 cells. hING4 can obviously inhibit proliferation and induce S phase reduction,G2/M phase arrest and cell apoptosis of SGC-7901. hING-4 can also down-regulate the expression of bcl-2 and up-regulate the expression of bax. Conclusion：hlNG4 can obviously inhibit proliferation and induces cell apoptosis of SGC-7901 cells. Down-regulating the expression of bcl-2 and up-regulating the expression of bax may be one of the molecular mechanisms involved in the anti-tumor effect.

关 键 词：ING4 腺病毒载体 基因治疗 胃癌 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]