HCTB006联合5-FU对胃癌细胞系MKN28、7901的作用及其机制  

Effect of combined HCTB006 and 5-fluorouracil on the growth of human gastric cancer cell lines SGC-7901 and MKN28

作　　者：张择伟[1] 宁守斌[2] 沈恩允 郭雷鸣 赵亚娟 王巧梅 

机构地区：[1]河北北方学院,河北省张家口市175000 [2]中国人民解放军北京空军总医院消化内科,北京市100142 [3]北京同为时代技术有限公司,北京市100176

出　　处：《世界华人消化杂志》2012年第7期546-551,共6页World Chinese Journal of Digestology

摘　　要：目的:探讨肿瘤坏死因子相关诱导配体受体(DR5)的单克隆抗体HCTB006联合5-FU对人胃癌细胞系7901、MKN28的作用以及机制.方法:用ATPlite法检测HBCT006单药组、5-FU单药组及两药物合用对胃癌细胞存活率的影响,研究两者之间的关系;采用流式细胞技术检测胃癌细胞系7901以及MKN28表面DR5的表达水平;Westernblot检测上述3组用药后胃癌细胞内XIAP,caspase3的变化.结果:胃癌细胞系7901、MKN28对HCTB006不敏感;5-FU对二者的增殖抑制作用具有时间以及浓度依赖效应;联合用药组具有很好的协同抑制胃癌细胞系增殖的效果,且具有浓度依赖效应,与给药次序无关.流式细胞技术检测胃癌细胞系7901,MKN28表面死亡受体DR5的表达依次为:93.8%以及87.7%.免疫迹印结果表明,联合用药组可以引发胃癌细胞内凋亡抑制蛋白XIAP的降解,激活最终凋亡执行蛋白caspase3,引起细胞死亡.结论:HTB006与5-FU联合应用具有协同杀伤胃癌细胞的作用.胃癌细胞7901、MKN28对于HCTB006的敏感程度与细胞表面DR5的表达量不相关;联合用药作用机制可能与细胞内抑制凋亡蛋白XIAP降解有关.AIM： To investigate the effect of combined antihuman death receptor 5 （DR5） monoclonal antibody HCTB006 and 5-fluorouracil （5-FU） on the growth of human gastric cancer cell lines SGC-7901 and MKN28 and to explore possible mechanisms involved. METHODS： The ability of HCTB006 and 5-FU, alone or in combination, to inhibit the proliferation of SGC-7901 and MKN28 cells was measured by ATP-Lite assay. The expression of DR5 on the surface of gastric cancer cells was examined by flow cytometry. The level of X-linked inhibitor of apoptosis （XIAP） and caspase 3 in treated cells was detected by Western blot. RESULTS： SGC-7901 and MKN28 cells were less sensitive to HCTB006. Concentrationand timedependent cytotoxicity of 5-FU was exhibited in SGC-7901 and MKN28 cells. The combination of 5-FU and HTCB006 exhibited a synergistic effect on the proliferation of SGC 7901 and MKN28 cells. The positive rates of DR5 expression on the surface of SGC-7901 and MKN28 cells were 93.8% and 87.7%, respectively. Western blot analysis revealed that combined HCTB006 and 5-FU induced XIAP degradation and caspase 3 activation. CONCLUSION： The combination of 5-FU and HTCB006 exhibited a synergistic effect on the growth of SGC-7901 and MKN28 cells possibly via a mechanism associated with XIAP degradation. The in vitro sensitivity of gastric cancer cells to HCTB006 has no direct association with DR5 expression.

关 键 词：死亡受体5 药物联合 连锁凋亡抑制蛋白 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]