O6-甲基鸟嘌呤DNA甲基转移酶在结肠癌干细胞中的表达及其与结肠癌5-氟尿嘧啶获得性耐药的关系  

Relationship between O6-methylguanine-DNA methytransferase expression in colon cancer stem cells and acquired 5-Fu chemotherapy drug resistance in colon cancer cells

作　　者：翟荣林[1] 张小明[1] 王继亮[1] 张万里[1] 龙跃平[1] 王国斌[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普外科,武汉430022

出　　处：《中华实验外科杂志》2014年第2期248-250,共3页Chinese Journal of Experimental Surgery

基　　金：教育部高等学校博士学科点专项科研基金资助项目（20110142120010）;湖北省自然科学基金资助项目（2011CDB378）

摘　　要：目的 探讨DNA修复蛋白O6-甲基鸟嘌呤DNA甲基转移酶（MGMT）在结肠癌干细胞中的表达及其与结肠癌5-氟尿嘧啶（5-Fu）获得性耐药的关系.方法 构建人结肠癌细胞5-Fu耐药模型,检测MGMT在耐药组与对照组中的表达差异,观察MGMT在CD133＋和CD133-细胞中的表达水平,比较耐药组和对照组CD133＋结肠癌干细胞分布比例.结果 MGMT在耐药组和对照组中的蛋白表达量分别为104.21±13.16和48.37±12.45,耐药组中的表达水平明显高于对照组（P＜0.01）;CD133＋细胞在耐药组和对照组中的比例分别为（1.77±0.75）％和（3.43±0.25）％,耐药组分布比例明显低于对照组;MGMT在耐药组和对照组CD133-细胞中的表达量均显著高于CD133＋细胞,耐药组与对照组之间的差异无统计学意义（P＞0.05）.结论 MGMT高表达与结肠癌5-Fu获得性耐药密切相关,耐药组中异常的CD133＋结肠癌干细胞分布比例提示其也参与了获得性耐药,但并不通过MGMT分子所介导.Objective To explore the relationship between DNA repair protein O6-methylguanineDNA methytransferase （MGMT） in colon cancer stem cells and acquired 5-fluorouracil （5-Fu） chemotherapy drug resistance in colon cancer cells.Methods Drug-resistance cell line model was induced by stepwise selection on exposure to increasing doses of 5-Fu in vitro.MGMT expression was detected in the model and the control groups as well as in the CD133 ＋ and CD133-colon cancer stem cells.Results MGMT relative protein expression in the model and the control groups was 104.21 ± 13.16 and 48.37 ± 12.45 respectively.MGMT expression in the model group was significantly higher than that in the control group （P 〈0.01）.The percentage of CD133 ＋ cells in the model group was （1.77 ± 0.75）%,obviously lower than （1.77 ±0.75）% in the control group.The MGMT expression in CD133-cells was obviously higher than that in CD133 ＋ cells in the model and the control group,but there was no significant difference between them.Conelusion MGMT and CD133 ＋ colon cancer stem cells may contribute to 5-Fu resistance in human colon cancer cells,but there was no relationship between the MGMT expression and percentage of CD133 ＋ colon cancer stem cells.

关 键 词：O6-甲基鸟嘌呤DNA甲基转移酶 结肠癌 5-氟尿嘧啶 化疗耐药性 

分 类 号：R735.3[医药卫生—肿瘤]