中国免疫学杂志2012,Vol.28Issue(12):1068-1072,5.DOI:10.3969/j.issn.1000-484X.2012.12.003
抗人DR5单克隆抗体诱导Jurkat和U937细胞凋亡的线粒体信号通路
Anti-human DR5 monoclonal antibody induced apoptosis in Jurkat/U937 cell by mitochondrial signal pathway
摘要
Abstract
Objective: To explore the mitochondrial Pathway in the apoptosis of Jurkat and U937 cells induced by anti-human DR5 monoclonal antibody-mDRA-6. Methods:The inhibition and apoptosis of Jurkat and U937 cells after treating with mDRA-6 or/ and caspases inhibitors were analyzed using MTT and FITC Annexin V/PI staining. The DNA ladder of Jurkat and U937 cells treated with mDRA-6(10 mg/L) for 6 h was analyzed by 1% agrose gel electrophoresis. The expression of bax, bcl-2, bcl-xl, Cyt c, caspase-9, caspase-3 of Jurkat and U937 cells after treating with mDRA-6 were detected by Western blot, respectively. Results:The proliferation of Jurkat and U937 cell after treating with mDRA-6 was inhibited in dose-dependent and time-dependent manner; DNA fragmentation detection indicated Jurkat and U937 cell apoptosis induced by mDRA-6. When the cells were treated with mDRA-6, analysis by immunoblotting indicated that bax and Cyt c was increased, while bcl-2 and bcl-xl was decreased in time dependent manner , caspases-9 and caspases-3 were activated in Jurkat and U937 cells. Jurkat and U937 cells were incubated with the inhibitors of caspase-9 for one hour, respectively, and then the cells were treated with mDRA-6, Jurkat and U937 cells inhibition induced by mDRA-6 were reduced by 24.36% (t =5.44, P < 0.01) and 20. 82% (t =4. 29 ,P < 0.01), Jurkat and U937 cells apoptosis induced by mDRA-6 were reduced by 32. 89% and 23. 97% , respectively. Conclusion: Anti-human DR5 monoclonal antibody-mDRA-6 induce the apoptosis of Jurkat and U937 cells through involves mitochondrial signal pathway.关键词
死亡受体5/单克隆抗体/凋亡/线粒体Key words
Death receptor 5/ Monoclonal antibody/ Apoptosis/ Mitochondria分类
医药卫生引用本文复制引用
李淑莲,蔡静,张舒曼,刘广超,马远方..抗人DR5单克隆抗体诱导Jurkat和U937细胞凋亡的线粒体信号通路[J].中国免疫学杂志,2012,28(12):1068-1072,5.基金项目
本文为国家 "重大新药创制" 科技重大专项 (No.2011ZX09506-004) (No.2011ZX09506-004)