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《奈達(dá)鉑體外誘導(dǎo)人卵巢癌順鉑耐藥細(xì)胞凋亡的機(jī)制-論文.pdf》由會(huì)員上傳分享,免費(fèi)在線閱讀,更多相關(guān)內(nèi)容在行業(yè)資料-天天文庫(kù)。
1、·1216·腫瘤防治研究2012年第39卷第10期doi:10.3971/J.issn.i000—8578.2012.10.013奈達(dá)鉑體外誘導(dǎo)人卵巢癌順鉑耐藥細(xì)胞凋亡的機(jī)制王莉,劉漢鋒,蔡正文,藍(lán)東,覃海園NedaplatinInducedApoptosisinHumanOvarianCancerCisplatin—resistantCellLinesinvitroandInvestigatedItsMechanismWangLi,LiuHanfeng,CaiZhengwen,1.a(chǎn)nDong,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:目的探討研究奈達(dá)鉑(NDP)體外對(duì)人卵巢癌順鉑原發(fā)耐藥細(xì)胞株sK()V3和繼發(fā)耐藥株SKOV3/DDP的抑制作用及其機(jī)制。方法采用MTT法檢測(cè)體外不同時(shí)間不同濃度的NDP對(duì)SKOV3及SKOV3/DDP細(xì)胞的殺傷作用,計(jì)算半數(shù)抑制濃度(ICs,);流式細(xì)胞術(shù)(FCM)測(cè)定給藥前后細(xì)胞凋亡率及周
7、期分布變化;半定量PCR分析凋亡基因Bcl一2,Bax,caspase3,caspase-9及反應(yīng)腫瘤細(xì)胞侵襲力的基因MMP一2的表達(dá)變化。結(jié)果NDP能明顯抑制sKOV3及sKOv3/DDP生長(zhǎng),呈時(shí)間一劑量依賴性;流式結(jié)果顯示隨時(shí)間、濃度增加,SKOV3和SK0V3/DDP細(xì)胞凋亡明顯增加,S期細(xì)胞的比例增加,差異均有統(tǒng)計(jì)學(xué)意義(P