榄香烯对人肝癌HepG-2细胞增殖及拓扑异构酶Ⅰ的影响  

Effects of elemene on proliferation and topoisomerase Ⅰ of human hepatocarcinoma HepG-2 cells

作　　者：龚敏[1] 梁鑫淼[2] 崔晓楠[1] 

机构地区：[1]大连医科大学附属第一医院肿瘤科,辽宁大连116011 [2]中科院大连化学物理研究所制药工程与过程化学研究中心,辽宁大连116023

出　　处：《中国癌症杂志》2011年第5期321-325,共5页China Oncology

基　　金：国家自然科学基金(No:30500586)

摘　　要：背景与目的:榄香烯(elemene,ELE)是传统抗肿瘤中药制剂,目前药效机制尚不明确。本研究旨在探讨ELE对人肝癌HepG-2细胞增殖及DNA拓扑异构酶Ⅰ(topoisomeraseⅠ,TOPOⅠ)的影响。方法:采用四甲基偶氯唑蓝还原法(MTT)观察ELE对HepG-2细胞增殖的影响;采用流式细胞术(FCM)检测ELE对HepG-2细胞周期的影响;采用RT-PCR法检测ELE对HepG-2细胞TOPOⅠmRNA表达的影响;采用TOPOⅠ介导的负超螺旋PBR322DNA解旋反应检测ELE对TOPOⅠ酶活性的影响;采用负超螺旋PBR322DNA检测ELE对DNA的直接抑制作用。结果:ELE能抑制HepG-2细胞增殖,其抑制效应具有时间和剂量依赖性;阻滞HepG-2细胞于S期,呈剂量依赖性;下调TOPOⅠmRNA表达,呈剂量依赖特性;对TOPOⅠ介导的负超螺旋PBR322DNA解旋反应有抑制作用;对负超螺旋PBR322DNA没有直接抑制作用。结论:ELE能够抑制HepG-2细胞增殖;影响TOPOⅠ的表达及活性可能是其作用机制之一。Background and purpose:The elemene(ELE) is a traditional Chinese antitumor drug.However,its mechanism is still unclear.The purpose of this study was to investigate the effects of ELE on the proliferation and topoisomerase Ⅰ(TOPO Ⅰ) of hepatocarcinoma HepG-2 cells.Methods:The cells proliferation were assessed by MTT assay.Cell cycles were shown through FCM.TOPOⅠmRNA expression was analyzed by RT-PCR.The activity of TOPOⅠ was measured by a TOPOⅠ mediated supercoiled PBR322 relaxation.The supercoiled PBR322 was also used to determine the direct DNA breakages.Results:ELE significantly inhibited HepG-2 cells proliferation in dose-and time-dependent ways,induced tumor cells arrested at the S-phase.Decreased TOPOⅠmRNA expression in dose-dependent ways,inhibited the TOPOⅠ mediated DNA relaxations,but could not directly induce DNA breakage at any concentrations.Conclusion:ELE could inhibit the proliferation of human hepatocellular carcinoma HepG-2 cells.The regulation of TOPOⅠ activity and mRNA expression might be one of the mechanisms of ELE anti-tumor.

关 键 词：榄香烯 TOPOⅠ 肝癌 HEPG-2细胞 PBR322DNA 

分 类 号：R73[医药卫生—肿瘤]