姜黄素对人肝癌耐药细胞株Bel7402/5-FU多药耐药性的逆转作用  

Curcumin reverses multidrug resistance of human hepatocellular carcinoma bel7402/5-FU cells

作　　者：曹仕琼[1] 李萍[1] 尹太勇[1] 杨盛力[2] 

机构地区：[1]华中科技大学同济医学院附属梨园医院消化内科,湖北省武汉市430077 [2]华中科技大学同济医学院附属梨园医院普通外科,湖北省武汉市430077

出　　处：《世界华人消化杂志》2012年第2期135-139,共5页World Chinese Journal of Digestology

基　　金：湖北省自然科学基金资助项目;No.2009CDB117~~

摘　　要：目的:探讨姜黄素对人肝癌耐药细胞株Bel7402/5-FU多药耐药性的逆转作用及可能的作用机制.方法:采用氟尿嘧啶(fluorouracil,5-FU)药物浓度梯度递增法诱导建立肝癌耐药细胞亚系Bel7402/5-FU;MTT法检测人肝癌细胞株Bel7402及其耐药细胞株Bel7402/5-FU对6种化疗药物以及姜黄素的敏感性;Western blot法检测Bel7402细胞、Bel7402/5-FU细胞及经过0、5、10、20mg/L姜黄素作用后的Bel7402/5FU细胞中多药耐药相关蛋白1(MRP1)、肺耐药相关蛋白(LRP)、P-糖蛋白(P-gp)、程序化死亡因子5(PDCD5)蛋白的表达水平.结果:Bel7402/5-FU细胞对6种化疗药物表现出交叉耐药性,其中对5-FU耐药指数最高;与Bel7402细胞相比,Bel7402/5-FU细胞中的MRP1、LRP、P-gp蛋白表达升高,PDCD5蛋白表达降低;随姜黄素浓度的升高,Bel7402/5FU细胞中MRP1、LRP、P-gp蛋白表达逐渐降低,PDCD5蛋白表达逐渐增高.结论:姜黄素具有逆转肝癌细胞多药耐药性的作用,可能与下调多药耐药相关蛋白MRP1、LRP、P-gp,上调凋亡相关蛋白PDCD5表达有关.AIM：To investigate whether curcumin reverses multidrug resistance of hepatocellular carcinoma drug-resistant cell line Bel7402/5-FU and to explore potential mechanisms involved.METHODS：The cell line Bel7402 was induced to form a multidrug resistant cell subline Bel7402/5-FU by exposing increasing concentra-tions of fluorouracil （5-FU）.The sensitivity of Bel7402 and Bel7402/5-FU cells to chemotherapeutics and curcumin were tested by MTT assay.The protein levels of multi-resistance related protein 1 （MRP1）,lung resistance-related protein （LRP）,p-glycoprotein （P-gp） and programmed cell death 5 （PDCD5） were detected by Western blotting in Bel7402 cells,Bel7402/5-FU cells and Bel7402/5-FU cells treated with different concentrations of curcumin.RESULTS：The Bel7402/5-FU cell line showed cross-resistance to six drugs,among which 5-FU had the highest RI.The protein expression levels of MRP1,LRP and P-gp in Bel-7402/5-FU cells were obviously higher than those in Bel7402 cells,while the expression of PDCD5 protein in Bel7402/5-FU cells was lower than that in Bel7402 cells.The expression of MRP1,LRP and P-gp proteins was down-regulated after curcumin treatment,while the PDCD5 protein was significantly increased.CONCLUSION：Curcumin can reverse multidrug resistance of the Bel7402/5-FU cell line via mechanisms possibly associated with downregulation of MRP1,LRP and P-gp expression and up-regulation of PDCD5 expression.

关 键 词：姜黄素 肝癌 多药耐药 

分 类 号：R735.7[医药卫生—肿瘤] R285[医药卫生—临床医学]