蛋白酶体抑制剂mg132对大肠癌细胞化疗增敏作用的研究.DOC

MG132对大肠癌HCT-8细胞的体外化疗增敏作用及机制 高伟艳1，申凤乾1，崔瑞雪1，裴迎新2，王贵吉1 1 郑州大学第一附属医院肿瘤科 郑州 450052 2 郑州大学公共卫生学院 郑州 450052 [摘 要] 目的 研究蛋白酶体抑制剂MG132联合奥沙利铂或伊立替康对大肠癌HCT-8细胞增殖和凋亡的影响及其机制。方法 奥沙利铂或伊立替康单药及联合MG132分别作用于HCT-8细胞,MTT法检测其对HCT-8细胞增殖的抑制作用，流式细胞术检测细胞凋亡率，免疫细胞化学检测NF-κB、caspase3蛋白表达。结果 联合蛋白酶体抑制剂MG132后，奥沙利铂、伊立替康对大肠癌HCT-8细胞增殖的抑制作用明显增强(P0.01)，细胞凋亡率增加(P0.01)，NF-κB表达降低而caspase3表达明显增高。结论 蛋白酶体抑制剂MG132能增强奥沙利铂、伊立替康抑制大肠癌HCT-8细胞增殖并诱导其凋亡。这可能与下调NF-κB表达、促进caspase3表达有关。 [关键词] 蛋白酶体抑制剂MG132；大肠癌；奥沙利铂；伊立替康；凋亡 [中图分类号] R73-36； R735.3+4 [文献标识码] A MG132 sensitizes HCT-8 cells to chemotherapeutic drugs and its mechanism GAO Wei-yan1，SHEN Feng-qian1，Cui Rui-xue1，PEI Ying-xin2，WANG Gui-ji1 1 Department of Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, P.R. China 2 Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, 450052, P.R. China [Abstract] Objective To study the effects and mechanism of proteasome inhibitor MG132 combined with oxaliplatin or irinotecan on growth and apoptosis in HCT-8 cells. Methods HCT-8 human colorectal cancer cells were treated with作者简介：高伟艳，女，河南省济源市，在读硕士，研究方向：恶性肿瘤的内科治疗。电话E-mail：weiyangaogao@126.com 通讯作者：王贵吉，电话：(0371 E-mail：pyx@ oxaliplatin or irinotecan singly contrast to associated with proteasome inhibitor MG132, the cell growth inhibitory rate was determined with MTT assay, apoptosis was detected by flow cytometry, expressions of nuclear factor-kappa B(NF-κB)p65 and caspase3 were detected by immunocytochemical technique. Results Compared with cells treated with oxaliplatin or irinotecan alone, cells treated with MG132 and oxaliplatin or irinotecan showed that the inhibition ratio of proliferation of cells was increased evidently (P0.01)，the apoptosis rate was also increased (P0.01 )；the expression of NF-κB was decreased, the expression of caspase3 was increased significantly. Conclusion Proteasome inhibitor MG132 could effectively increase the cytotoxicity of oxalipla