衣霉素增强胃腺癌细胞对TRAIL诱导凋亡的敏感性  

Tunicamycin sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-R2

作　　者：程文晋[1] 吴萍[1] 陈思[1] 江蓓蕾[1] 叶艳[1] 张旭东[1] 张林杰[1] 

机构地区：[1]安徽医科大学免疫学教研室,合肥230032

出　　处：《安徽医科大学学报》2008年第2期119-123,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金项目(编号:30572118);安徽医科大学07年校科研基金项目(编号:522566);安徽省自然科学基金(编号:070413077)

摘　　要：目的探讨衣霉素对TRAIL(TNF-related apoptosis-in-ducing ligand)诱导的胃腺癌细胞的凋亡的作用。方法PI染色流式细胞仪检测衣霉素与TRAIL作用于细胞前后细胞凋亡率的变化;双抗体流式细胞仪检测药物作用前后细胞表面TRAIL受体表达情况;W estern b lot检测药物作用前后caspase蛋白水平的变化;JC-1染色流式细胞仪检测药物作用前后线粒体膜电位的变化。结果衣霉素可明显增加TRAIL诱导的胃腺癌细胞凋亡率;衣霉素作用于胃腺癌细胞后,细胞表面TRAIL-R2表达明显增高;衣霉素促进TRAIL诱导的胃腺癌细胞caspase-3、PARP活化和线粒体膜电位减少。结论衣霉素可通过上调细胞表面TRAIL受体表达来增强胃腺癌细胞对TRAIL诱导的凋亡的敏感性,这种致敏性与激活caspase级联反应和线粒体膜电位减少有关。Objective To explore the effect of tunicamycin on TRAIL-induced apoptosis in human gastric adeno-carcinoma cells and its mechanism. Methods Apoptosis was measured with flow cytometry using propidium iodide staining before and after Tunicamycin and TRAIL treatment. The expression of TRAIL receptors on the cell surface were measured with flow cytometry before and after Tunicamycin treatment. With or without treatment with Tunica- mycin and TRAIL,the expression of caspase at protein level was measured by Western blot analysis;mitochondrial membrane potential was measured using JC-1 by flow cytometry. Results Gastric adenocarcinoma cells were relatively resistant to ER-stress induced apoptosis;Tunicamycin sensitized melanoma cells to TRAIL-induced apoptosis. Tunicamycin up-regulated cell surface expression of TRAIL-R2 in gastric adenocarcinoma cells. Tunicamycin pro-moted TRAIL-induced caspase activation, including caspase-3, PARP. Tunicamycin promotes TRAIL-induced reduction in mitochondrial membrane potential. Conclusion Tunicamycin sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis by up-regulating of TRAIL-R2. Tunicamycin-mediated sensitization is associated with increased activation of the caspase cascade and reduction in mitochondrial membrane potential.

关 键 词：胃肿瘤 细胞凋亡 衣霉素 

分 类 号：R735.2[医药卫生—肿瘤] R329.2[医药卫生—临床医学]