三氧化二砷诱导口腔鳞癌细胞凋亡的机制探讨

目的：探讨三氧化二砷诱导口腔鳞癌细胞凋亡的机制。方法：通过对两种舌鳞癌细胞系OSC－19，Tca8113经三氧化二砷作用后电镜下形态学改变、流式细胞仪测得的细胞周期变化、线粒体跨膜电位改变、凋亡相关蛋白BCL－2、p16、p53、Caspase-3及PARP变化；初步探讨三氧化二砷诱导舌鳞癌细胞系凋亡的机制。结果：（1）三氧化二砷抑制口腔鳞癌细胞生长通过毒性损伤和诱导凋亡双重途径来实现；（2）经三氧化二砷作用后，western blot检测bcl-2、p53、p16基因表达蛋白无变化，而caspase-3,PARP发生改变；（3）经三氧化二砷作用后，两类舌鳞癌细胞系线粒体跨膜电位明显下降，细胞周期G2－M期阻滞，且与凋亡产生同步。结论：（1）线粒体和微管可能是三氧化二砷的主要作用位点，为三氧化二砷发挥凋亡诱导效应的启动因素；（2）Caspase-3途径的激活可能为三氧化二砷诱导口腔鳞癌细胞凋亡的关键途径之一。

Investigation of apoptosis mechanism of arsenic trioxide on oral squamous cell carcinoma

Objective To probe the possible mechanism of growth inhibitory and apoptosis of oral squamous cell carcinoma by arsenic trioxide Methods The induction of apoptosis in two tongue squamous carcinoma cells treated by arsenic trioxide was investigated The morphology changes of the cells was observed under electron microscope The mitochondrial transmembrane potential was detected using rhodamine 123 and flow cytometry The cell cycle was detected by flow cytometry,and p16, p53, BCL 2, Caspase 3, and PARP changes were eyamined by western blot Results 1 The antiproliferative effect on the oral squamous carcinoma cells by arsenic trioxide was carried out through two ways: induction of apoptosis and toxicity damage 2 Activation of the caspase 3 and PARP, while no changes of p16, p53, BCL 2 occurred 3 Mitochondrial transmembrane potential collapse and G 2 M stagnation were correlated with apoptosis of oral squamous cell carcinoma Conclusions 1 Tubulins and mitochondria may bethe chief action position of arsenic trioxide, which is the start up factors of mechanism 2 Activation of the caspase 3 proteolytic pathway may be one of the pivotal ways of apoptosis procedure induced by arsenic trioxide