hCTB006联合伊立替康对胃癌细胞BGC823、SGC7901协同杀伤的作用机制  

Synergistic cytotoxic effect of anti-human DR5 monoclonal antibody hCTB006 and irinotecan on gastric cancer BGC823 and SGC7901 cells

作　　者：王晓[1] 宁守斌[2] 沈恩允 郭雷鸣 

机构地区：[1]河北北方学院 [2]中国人民解放军空军总医院消化内科,北京市100142 [3]北京同为时代生物技术有限公司,北京市100176

出　　处：《世界华人消化杂志》2012年第32期3130-3134,共5页World Chinese Journal of Digestology

摘　　要：目的:研究人死亡受体(death receptor5,DR5)激动型抗体hCTB006联合伊立替康对不同分化程度胃癌细胞BGC823、SGC7901的体外抑瘤作用,并对其诱导胃癌细胞凋亡的机制进行初步探讨.方法:实验将BGC823、SGC7901细胞分为伊立替康组、hCTB006组和两者联合应用组,应用ATPlite法研究各组药物的体外抑瘤作用;采用ELISA法研究伊立替康处理胃癌细胞前后DR5表达的变化.采用Western blot技术检测药物处理前后BGC823、SGC7901细胞X-联锁凋亡抑制蛋白(X-chromosome-linked inhibitory of apoptosis protein,XIAP)的表达变化情况.结果:BGC823对hCTB006中度敏感,对SGC7901不敏感,伊立替康对胃癌细胞的增殖抑制作用呈浓度依赖性,与hCTB006联合用药后对BGC823具有良好的协同抑制作用,但对SGC7901协同作用不明显.ELISA测得伊立替康处理后胃癌细胞DR5的表达量无明显变化.但伊立替康和hCTB006联合用药可使胃癌细胞BGC823内XIAP水平明显降低,而对SGC7901细胞内XIAP没有明显作用.结论:伊立替康联合hCTB006后对低分化胃癌细胞BGC823的增殖有明显协同抑制作用,而对中度分化的SGC7901细胞呈拮抗作用,这种诱导胃癌细胞凋亡的机制可能与其DR5的表达无关,而与联合作用后细胞抑凋亡蛋白XIAP的表达水平有关.AIM：To explore the cytotoxic effect of combined anti-human DR5 monoclonal antibody hCTB006 and irinotecan on human gastric cancer BGC823 and SGC7901 cells in vitro.METHODS：The cytotoxic effect of hCTB006 and irinotecan,alone or in combination,was evaluated using ATP lite assay.DR5 expression in tumor cells was examined using ELISA.The level of cytoplasmic XIAP was detected by Western blot.RESULTS：Irinotecan exerted a cytotoxic ef-fect on gastric cancer cells in a concentrationdependent manner,while the effect of hCTB006 on gastric cancer cells was not concentrationdependent.hCTB006 combined with irinotecan resulted in a synergistic cytotoxic effect on BGC823 cells,but not on SGC7901 cells.Irinotecan treatment did not significantly alter DR5 expression.Combined irinotecan and hCTB006 down-regulated XIAP expression in BGC823 cells,but not in SGC7901 cells.CONCLUSION：Irinotecan can inhibit the growth of gastric cancer dose-dependently.Antihuman DR5 monoclonal antibody hCTB006 and irinotecan exert a synergistic cytotoxic effect on gastric cancer cells possibly by regulating the expression of XIAP.

关 键 词：胃癌细胞 肿瘤坏死因子相关诱导配体受体 死亡受体5 X-联锁凋亡抑制蛋白 伊立替康 协同增效 

分 类 号：R735.2[医药卫生—肿瘤]