下调X连锁凋亡抑制蛋白基因表达增强结肠癌细胞对5-氟尿嘧啶敏感性的研究  

Downregulation of XIAP gene expression increases sensitivity of colon cancer cells to 5-fluorouracil

作　　者：周保国[1] 魏争[1] 孙学溥[1] 乔海泉[1] 

机构地区：[1]哈尔滨医科大学附属第一医院普外四科,150001

出　　处：《中华普通外科杂志》2011年第1期45-47,共3页Chinese Journal of General Surgery

基　　金：黑龙江省青年科学技术专项基金（QC07C96）;哈尔滨医科大学附属第一医院科研基金（2007053）

摘　　要：目的 观察下调X连锁凋亡抑制蛋白（X-linked inhibitor of apoptosis protein,XIAP）基因表达后结肠癌细胞对5-氟尿嘧啶（5-Fu）敏感性的变化.方法 采用脂质体包裹方法将携带靶向干扰XIAP序列的表达载体转染人结肠癌细胞HCT-8和HCT116,观察结肠癌细胞生长活性的变化;应用5-Fu后,观察结肠癌细胞对5-Fu敏感性的变化,并应用蛋白印迹方法检测结肠癌细胞内凋亡相关因子caspase-3的活性变化. 结果抑制XIAP基因表达后,结肠癌细胞HCT-8和HCT116的生长活性受到有效抑制;结肠癌细胞HCT-8对5-Fu的耐药性得到逆转（P＜0.01）,HCT116对5-Fu的敏感性得到明显提高（P＜0.05）;结肠癌细胞内caspase-3的表达活性提高,5-Fu诱导细胞凋亡的活性得到增强. 结论XIAP的表达是结肠癌细胞HCT-8和HCT116对5-Fu耐药的一个重要机制;抑制XIAP基因表达后能够增强结肠癌细胞HCT-8和HCT116对5-Fu化疗的敏感性.Objective To investigate sensitivity of colon cancer cells to 5-fluorouracil after downregulation of XIAP gene expression. Method Colon cancer cells HCT-8 and HCT116 were transfected with a short hairpin RNA targeted to XIAP by liposome, cells viability were examined.5-fluorouracil was applied into two kinds of colon cancer cells. Tumor cells sensitiviy to chemotherapeutic drug was evaluated. Caspase-3 activity in tumor cells was examined by Western blot. Result After downregulation of XIAP expression, cell growing viability of these two kinds of colon cancer cells was restricted, HCT-8 resistance to 5-fluorouracil was reversed （ P 〈 0. 01 ）, HCT116 sensitivity to 5-fluorouracil was enhanced （P 〈 0.05）, caspase-3 expression in colon cancer cells was highly activated, apoptosis inducing activity of 5-fluorouracil was increased significantly. Conclusions XIAP expression was a important mechanism in colon cancer cells HCT-8 and HCT 116 resistant to 5-fluorouracil, sensitivity to 5-fluorouracil of HCT-8 and HCT-116 was increased by downregulation of XIAP expression.

关 键 词：结肠肿瘤 基因表达 氟尿嘧啶 抗药性 肿瘤 RNA干扰 

分 类 号：R735.35[医药卫生—肿瘤]