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亚硒酸钠通过线粒体途径诱导人胃癌SGC-7901细胞凋亡的机制
Sodium selenite induces apoptosis of human gastric cancer SGC-7901 cells through mitochondrial-dependent pathway
目的 通过检测亚硒酸钠诱导人胃癌SGC-7901细胞系凋亡过程中Bax/Bcl-2、线粒体膜电位和细胞色素C（Cyt C）表达的变化，探讨亚硒酸钠诱导胃癌细胞凋亡的作用机制。 方法 将人胃癌细胞系SGC-7901 细胞加入不同浓度亚硒酸钠(2.5、5.0、10.0mol/L)的培养液中培养24h、48h，免疫细胞化学法和免疫印迹法(Western blotting)检测Bax/Bcl-2蛋白的表达；以罗丹明123（rhodamine123）为细胞染色剂，采用流式细胞技术检测细胞的线粒体膜电位的变化；Western blotting检测细胞质Cyt C和线粒体Cyt C蛋白含量的变化。 结果 免疫细胞化学法和Western blotting检测结果显示，亚硒酸钠能够能够提高Bax蛋白的表达（P<0.05）、降低Bcl-2蛋白的表达（P<0.05），且呈剂量依懒性；流式细胞术结果显示，亚硒酸钠能够降低细胞线粒体膜电位；提示：亚硒酸钠可以通过改变Bax、Bcl-2蛋白的含量，降低线粒体的膜电位来诱导细胞凋亡。Western blotting检测结果显示，亚硒酸钠能够提高细胞质Cyt C蛋白的表达（P<0.05）并降低线粒体内Cyt C蛋白的表达（P<0.05），促使线粒体内的Cyt C向细胞质内释放。 结论 亚硒酸钠通过上调Bax并下调Bcl-2蛋白表达，降低线粒体膜电位，促进Cyt C从线粒体释放到细胞质，通过线粒体途径诱导人胃癌SGC-7901细胞凋亡。
Objective To study the mechanism of gastric cancer cells apoptosis induced by sodium selenite，by investigating the expression of Bax/Bcl-2, the change of mitochondrion membrane potential and cytochrome C(Cyt C) in the process apoptosis ofof human gastric cancer SGC-7901 cells. Methods Human gastric cancer SGC-7901 cell line was added different concentrations (2.5, 5.0, 10.0μmol/L) of sodium seleite for 24hours,48hours. The expression of Bax/Bcl-2 protein was detected by immunocytochemical and Western blotting methods. SGC-7901 cells were stained by Rhodamine123 to detect changes of mitochondrion membrane potential by flow cytometry. The changes of cytoplasm Cyt C and mitochondria Cyt C protein content were detected by Western blotting. Results Immunocytochemistry and Western blotting showed that sodium selenite increased the Bax protein levels(P<0.05) and reduced the Bcl-2 protein levels (P<0.05) in dose-dependent manner.Flow cytometry technique results showed that sodium selenite reduced mitochondrial membrane potential(P<0.05). The results indicated that sodium selenite may induce SGC-7901 cells apoptosis by altering Bax/Bcl-2 and reducing mitochondrial membrane potential. Western blotting showed that sodium selenite increased the cytoplasm Cyt C protein levels(P<0.05) and reduced the mitochondria Cyt C protein levels (P<0.05), therefore promoted the release of Cyt C to cytoplasm. Conclusion Sodium selenite can induce apoptosis of human gastric cancer SGC-7901 cells by increasing Bax and discreasing Bcl-2 gene expression, reduce the mitochondrial membrane potential, to promote Cyt C release from mitochondria to the cytoplasm, and induce human gastric cancer SGC-7901 cell apoptosis through mitochondrial-dependent pathway.
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国家自然基金资助项目;山东省自然基金
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