奈达铂体外诱导人卵巢癌顺铂耐药细胞凋亡的机制-论文.pdf

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1、·1216·肿瘤防治研究2012年第39卷第10期doi：10．3971／J．issn．i000—8578．2012．10．013奈达铂体外诱导人卵巢癌顺铂耐药细胞凋亡的机制王莉，刘汉锋，蔡正文，蓝东，覃海园NedaplatinInducedApoptosisinHumanOvarianCancerCisplatin—resistantCellLinesinvitroandInvestigatedItsMechanismWangLi，LiuHanfeng，CaiZhengwen，1．anDong，QinHaiyuanDepartmentofMedicalOocology，TheFi

2、rstAffiliatedHospitalofGuangxiMedicalUniversity，Nanning，530007，ChinaCorrespondingAuthor：LiuHanfeng，E-mail：237／)78725q．cornAbstract：ObjeetiveTostudyinhibitionofnedaplatin(NDP)onhumanovariancancercelllinesSKOV3withintrinsiccisplatin—resistanceandSKOV3／DDPwithacquiredcisplatin—resistanceandinvest

3、igateitsmechanism．MethodsMTTassaywasusedtoevaluatetheinhibitionindifferentconcentrationandtime0fNDPtreatmentonSKOV3andSKOV3／DDPcells，thencalculatedinhibitoryconcentration(IC．．．)．Cellapoptosisandcycleweredetectedbyflowcytometry(FCM)．ThechangesofBcl2，Bax，caspase-3，caspase-9．MMP-2inmRNAlevelswere

4、quantifiedbyRT—PCR．ResultsNDPinhibitedthegrowthofSKOV3andSKOV3／DDPcellssignificantlyintimeanddose-dependentmanner．TheresultfromFCMshowedthatapoptoticrateandthepercentageofS-phasecellstendtoincreaseintimeandconcentrationofnedaplatindependentmanner(P<0．05)．Comparedwithcontrolgroups，therewereadec

5、reaseinBcl2andMMP-2mRNAexpression，butanincreaseinBax，caspase一3andcaspase-9．ConclusionNDPcaninhibitproliferationofSKOV3andSKOV3／DDPcells．Theeffectmaybeascribedtoinducingcellapopto—sis，theS-phasearrestandthedownregulationofBcl2，MMP一2expression，up—regulationofBax，caspase一3andcaspase-9expression．N

6、DPcansuppressMMP2expression，soitmaybecanreduceinvasionforceofovariancancer．Keywords：Nedaplatin；SKOV3；SKOV3／DDP；Cellapoptosis；Cisplatinresistance摘要：目的探讨研究奈达铂(NDP)体外对人卵巢癌顺铂原发耐药细胞株sK()V3和继发耐药株SKOV3／DDP的抑制作用及其机制。方法采用MTT法检测体外不同时间不同浓度的NDP对SKOV3及SKOV3／DDP细胞的杀伤作用，计算半数抑制浓度(ICs，)；流式细胞术(FCM)测定给药前后细胞凋亡率及周

7、期分布变化；半定量PCR分析凋亡基因Bcl一2，Bax，caspase3，caspase-9及反应肿瘤细胞侵袭力的基因MMP一2的表达变化。结果NDP能明显抑制sKOV3及sKOv3／DDP生长，呈时间一剂量依赖性；流式结果显示随时间、浓度增加，SKOV3和SK0V3／DDP细胞凋亡明显增加，S期细胞的比例增加，差异均有统计学意义(P