结肠癌细胞获得性5氟尿嘧啶耐药的机制研究  

Possible mechanisms of acquired resistance to 5-FU in human colon cancer

作　　者：朱玉萍[1] 何超[1] 朱洪波[1] 毛伟芳[1] 黄学锋[1] 

机构地区：[1]浙江大学医学院附属邵逸夫医院肛肠外科及临床医学研究所,浙江杭州310016

出　　处：《中国病理生理杂志》2007年第10期2007-2011,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30271467No.30528030);浙江省自然科学基金资助项目(No.Y205093)

摘　　要：目的:探讨结肠癌细胞获得性5氟尿嘧啶耐药的机制。方法:建立5-FU耐药的结肠癌细胞,通过免疫印迹法检测多种耐药相关蛋白的表达,分析耐药的可能机制。结果:反复用5-FU处理结肠癌DLD1和DLD1-TRAIL/R细胞,得到5-FU耐药的DLD1-5-FU/R和DLD1-TF/R细胞,进一步研究发现,5-FU不能诱导耐药细胞发生S期停滞和DNA损伤。接着发现耐药细胞中有过表达的Bik、Bcl-Xs和Bcl-XL蛋白,而DLD1亲代细胞过表达Bcl-XL后,能够部分抵抗5-FU诱导的凋亡,但仍不能耐受5-FU诱导的S期停滞和DNA损伤。结论:过表达的Bcl-XL蛋白对结肠癌细胞获得性5-FU耐药具有一定作用,但过表达Bcl-XL不影响5-FU诱导的DNA损伤和细胞周期的改变,这提示结肠癌获得性5-FU耐药还存在着Bcl-XL之外的其它机制。AIM ： To explore the mechanisms of resistance to 5 - fluorouracil （5 - FU ） in human colon cancer cells. METHODS ： 5 - FU - resistant cell lines were established and their IC50 were calculated by detection of cell survival rate. Western blotting was performed to analyze the expression of several proteins, by which the possible mechanisms of acquired resistance to 5 - FU were determined in human colon cancer cells. RESULTS. The resistant cells were resistant to 5 - FU - induced S phase arrest as well as the expression of DNA damage marker - phosphor - histone H2A. X. Furthermore, data demonstrated that over - expression of Bik, Bcl - Xs, and Bcl - XL proteins were observed in 5 - FU - resistant cell lines. However, the DLD1/Bcl - XL cells were only partially resistant to 5 - FU - induced apoptosis, but not 5 - FU - induced S phase arrest and phosphor -histone H2A. X. CONCLUSION： Over - expression of Bcl - XL protein certainly contributes to acquired 5 - FU resistance in human colon caners, but has no effect on 5 - FU - induced DNA damage and cell cycle disorder, suggesting that other mechanisms are involved in acquired resistance to 5 - FU in human colon cancer.

关 键 词：氟尿嘧啶 抗药性 结肠肿瘤 蛋白质Bcl—XL 

分 类 号：R363[医药卫生—病理学]