五味子酯乙对肺癌耐紫杉醇A549/Tax细胞的多药耐药逆转作用及机制  

Schisantherin B Reverses Multidrug Resistance of Lung Cancer A549/Tax Cells And Its Underlying Mechanism

作　　者：刘小东 郑小红[1] 张稳稳 Liu Xiaodong;Zheng Xiaohong;Zhang Wenwen(Chongqing Medical and Pharmaceutical College,Chongqing401331,China)

机构地区：[1]重庆医药高等专科学校药学院,重庆401331

出　　处：《山东化工》2020年第14期27-30,共4页Shandong Chemical Industry

基　　金：重庆市自然科学基金项目(cstc2018jcyjAX0722);重庆市教委青年项目(KJQN201802805,KJQN201902801);重庆医药高等专科学校人才引进项目(ygz2018301)。

摘　　要：目的:研究探讨五味子酯乙对肺癌耐紫杉醇A549/Tax细胞的肿瘤多药耐药(MDR)逆转作用及机制。方法:MTT法检测分析五味子酯乙单独或联用阿霉素、紫杉醇对耐药A549/Tax细胞及其亲本敏感A549细胞的细胞毒性及MDR逆转作用,阿霉素蓄积实验和Pgp-Glo TM Assay Systems分析检测五味子酯乙对P糖蛋白(P-gp)外排功能及P-gp ATPase活性的影响,Westen blot检测分析A549/Tax细胞中P-gp和β-actin的蛋白水平。结果:五味子酯乙(1.0、2.5、5.0μmol/L)剂量依赖性提高紫杉醇和阿霉素对P-gp过表达的A549/Tax细胞的抗增殖活性,激活P-gp ATPase活性并底物竞争性的抑制P-gp的药物外排转运功能,下调P-gp的过表达。结论:五味子酯乙通过底物竞争性抑制P-gp的药物外排功能和下调其蛋白水平有望在临床中克服P-gp过表达介导的MDR。Objective:This study aimed to evaluate the multidrug resistance reversal effect of schisantherin B in lung cancer A549/Tax cells and its underlying mechanism.Methods:Cytotoxicity and reversal activity of schisantherin B in A549/Tax cells and its parental A549 cells were measured by MTT assay.The intracellular accumulation of p-glycoprotein(P-gp)substrate doxorubicin and ATPase activity of P-gp were detected by flow cytometry and Pgp-Glo TM assay systems.The expression of P-gp andβ-actin were determined by Western blot.Results:Results showed that schisantherin B(1.0,2.5,5.0μmol/L)significantly enhanced the cytotoxicity of taxol and doxorubicin in P-gp-overexpressed A549/Tax cells in a dose-dependent manner.It also significantly increased intracellular doxorubicin accumulation and activiated the P-gp ATPase activity.Moreover,schisantherin B significantly down-regulated P-gp expression.Conclusion:These findings suggest that schisantherin B may be a promising agent for overcoming P-gp-mediated MDR in clinic.

关 键 词：肿瘤多药耐药 P糖蛋白 五味子酯乙 外排功能 

分 类 号：TK730.2[交通运输工程—轮机工程] O357.5[动力工程及工程热物理—流体机械及工程]