水通道蛋白AQP2在原发性肝细胞肝癌多柔比星耐药机制中的作用研究  

Effect of Aquaporins 2 on drug resistance of doxorubicin in the primary hepatocellular carcinoma

作　　者：叶龙云[1] 潘洁雪[1] 余正平[1] YE Long-yun;PAN Jie-xue;YU Zheng-ping(Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China)

机构地区：[1]温州医科大学附属第一医院肝胆外科,浙江温州325000

出　　处：《肝胆胰外科杂志》2017年第2期145-148,共4页Journal of Hepatopancreatobiliary Surgery

基　　金：浙江省中医药管理局青年人才基金项目(2017ZQ020);浙江省医药卫生科技计划项目(2017KY462);浙江省科技厅公益项目(2016C37127);温州市科技局项目(Y20160037)

摘　　要：目的探索原发性肝细胞肝癌(HCC)多柔比星(doxorubicin,DOX)耐药的机制,为进一步提高HCC患者介入治疗的疗效提供前期探索。方法应用Western blotting方法检测DOX处理后的上皮间质化转变(EMT)的相关蛋白E-Cadherin和Vimentin表达情况,使用流式细胞仪观察细胞干性标记CD133的变化情况,使用基因芯片技术观察DOX处理后的细胞机制变化。结果 DOX能诱导HCC细胞发生上皮间质化转变,并且能提升HCC细胞CD133的比例(3.5%vs 35.5%,P<0.05);基因芯片提示HCC细胞内水通道蛋白AQP2基因显著上调;敲降AQP2基因后,能显著减弱DOX诱导HCC细胞产生EMT的效果。结论水通道蛋白AQP2在肝细胞肝癌多柔比星耐药机制中具有重要作用,降低AQP2的表达可以减弱多柔比星诱导肝癌细胞上皮间质化转变的效果。Objective To investigate the mechanisms of doxorubicin resistance in hepatocellular carcinoma(HCC),and to provide preliminary exploration on improving the effect of transhepatic arterial chemotherapy andembolization(TACE)in HCC patients.Methods The expression of epithelial-mesenchymal transition(EMT)related proteins,E-Cadherin and Vimentin were detected by Western blotting.Flow cytometry was used to evaluatethe level of CD133.Furthermore,the precise mechanisms under doxorubicin treatment was analyzed by microarray.Results Doxorubicin could significantly induce EMT in HCC cells.Besides,the expression of CD133was also increased(3.5%vs35.5%,P<0.05).The microarray data suggested that Aquaporins2(AQP2)increasedmost dramatically among AQPs under doxorubicin treatment.In addition,knockdown of AQP2significantly attenuatedthe induction of EMT.Conclusion AQP2plays an important role in doxorubicin resistance in HCC.Knockdown of AQP2may reduce the doxorubicin-induced EMT.

关 键 词：原发性肝细胞肝癌(HCC) 多柔比星(DOX) 上皮间质化转变 水通道蛋白AQP2 

分 类 号：R735.7[医药卫生—肿瘤]