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Anti-tumor effects of Apoptin gene on human gastric carcinoma BGC-823 and its correlation with apoptotic signal transduction
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- Author:
- No author available
- Journal Title:
- WORLD CHINESE JOURNAL OF DIGESTOLOGY
- Issue:
- 31
- DOI:
- 10.3969/j.issn.1009-3079.2006.31.002
- Key Word:
- Apoptin基因;胃癌;BGC-823细胞系;细胞凋亡;抗肿瘤效应
Abstract： 目的:探讨Apoptin基因对人胃癌细胞BGC-823的抑制作用及其参与胞内细胞信号转导的机制.方法:应用脂质体转染法将重组质粒pVAX1-Apoptin体外转染BGC-823细胞,运用噻唑兰(methyl thiazolyl tetrazolium,MTT)分析法检测重组质粒对BGC-823肿瘤细胞的抑制作用;通过AO/EB染色法对pVAX1-Apoptin转染的肿瘤细胞进行形态学观察;运用流式细胞术检测细胞线粒体跨膜电位(△Ψm);通过免疫印迹检测细胞色素c(cytochrome c,Cyto c)释放;应用底物显色法检测Caspase-3/9活性.结果:pVAX1-Apoptin转染比pVAX1具有更强的抑瘤效应(10 μg质粒转染72 h后,23.37%vs99.61%,P＜0.01),并且肿瘤细胞的死亡方式以凋亡为主.实验结果显示,pVAX1-Apoptin转染导致细胞线粒体跨膜电位下降,与pVAX1转染BGC-823细胞相比有显著差异(46.7%±7.26% vs 70.66%±5.98%,P＜0.01);同时伴随细胞色素c的释放.另外,pVAX1-Apoptin和pVAX1转染细胞的Caspase-3/9活性具有显著差异(Caspase-9:0.181±0.032 vs 0.079±0.013,P＜0.01;Caspase-3:0.242±0.041 vs 0.058±0.023,P＜0.01).结论:pVAX1-Apoptin转染BGC-823肿瘤细胞导致线粒体跨膜电位下降,并刺激释放细胞色素c,从而激活Caspase-9.经细胞色素c激活的Caspase-9进而活化凋亡通路下游关键作用因子,并对BGC-823肿瘤细胞产生抑制效应.
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