丹参酮IIA增强顺铂抗前列腺癌作用及分子机制研究-论文.pdf

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1、药学学报ActaPharmaceuticaSinica2013，48(5)：675—679·675·丹参酮IIA增强顺铂抗前列腺癌作用及分子机制研究侯莉莉，许秋菊，胡国强，谢松强(河南大学化学生物学研究所，河南开封475004)摘要：探讨丹参酮IIA增强顺铂抗前列腺癌作用及其分子机制。采用MTT法检测细胞增殖，流式细胞仪检测细胞周期变化及凋亡率，Westernblotting检测蛋白的表达水平，高效液相色谱法检测细胞内顺铂含量。结果表明：丹参酮IIA通过增加细胞内顺铂浓度从而产生协同抗细胞增殖作用，两者联用可诱导LNCaP及PC3细胞周期阻滞于S期并引起细胞凋亡，caspase及Bc1．

2、2家族成员均参与了该凋亡过程。提示丹参酮IIA能明显增强顺铂的抗前列腺癌作用，并对激素依赖性和非依赖性前列腺癌均有效。关键词：丹参酮IIA=顺铂：细胞周期：细胞凋亡：增效作用中图分类号：R963文献标识码：A文章编号：0513-4870(2013105—0675．05SynergisticantitumoreffectsoftanshinoneIIAincombinationwithcisplatinviaapoptosisintheprostatecancercellsHOULi—li，XUQiu-ju，HUGuo．qiang，XIESong—qiang(InstituteofChem

3、icalBiology,HenanUniversity,Kaifeng475004,China)Abstract：TreatmentwiththecombinationofChineseherbsandcytotoxicchemotherapiesshowedahighersurvivalrateinclinicaltrials．Inthisreport．theresultsdemonstratedthatthetanshinoneIIA。akeycomponentofSalviamiltiorrhizabunge，whenitiscombinedwiththecytotoxicdrug

4、cisplatinshowedsynergisticantitumorefectsonhumanprostatecancerPC3cellsandLNCaPcellsinvitro．AntiproliferativeeffectsweredetectedwithMTTassa~Cellcycledistributionandapoptosisweredetectedbyflowcytometer．ProteinexpressionwasdetectedbyWesternblotting．Theintracellularconcentrationofcisplatinwasdetected

5、byhighperformanceliquidchromatography．TheresultsdemonstratedthattanshinoneIIAsignificantlyenhancedtheantiproliferativeeffectsofcisplatinonhumanprostatecancerPC3cellsandLNCaPcellswiththeincreaseoftheintracellularconcentrationofcisplatin．TheseefectswerecorrelatedwithcellcyclearrestedatSphaseandcell

6、apoptosis．Theapoptosismightbeachievedthroughdeathreceptorpathwayandmitochondrialpathway．Furthermore，theBcl-2familymemberswerealsoinvolvedinthisapoptoticprocess．Collectively,theseresultsindicatedthatthecombinationoftanshinoneIIAandcisplatinhadabettertreatmentefectinvitronotonlyonandrogen-dependent

7、LNCaPcellsbutalsoonandrogen-independentPC3cells．Keywords：tanshinoneIIA；cisplatin；cellcycle；apoptosis；synergism前列腺癌是老年男性常见的恶性肿瘤之一，在欧美地区发病率很高，占男性恶性肿瘤的第2位：虽然前列腺癌在我国发病率较低，但随着老年人口的增加，有逐年增加的趋势。在男性泌尿生殖系统恶性收稿日期：2012．I1．06；修回日期