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

摘要

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.%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.