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1、24现代生物医学进展ProgressinModernBiomedicine2006Vol.6No.2PPAR激动剂罗格列酮对人乳腺癌细胞生长抑制及诱导凋亡作用研究陆海波张清媛周建华王影鲁海玲(哈尔滨医科大学附属肿瘤医院哈尔滨150040)摘要目的:观察氧化酶体激活物增殖受体(PPAR)激动剂罗格列酮(ROZ)在体外激活PPAR后对MCF-7细胞的生长抑制及诱导凋亡作用。方法:MTT法检测ROZ对MCF-7细胞的生长抑制作用;集落形成实
2、验观察ROZ对MCF-7细胞集落形成的影响;不同浓度ROZ作用72h,Hoechst33342染色观察MCF-7细胞的形态变化,流式细胞光度分析术(FCM)检测凋亡细胞百分率以及ROZ对细胞周期的影响;Westernblot方法检测ROZ对MCF-7细胞Bcl-2、Caspase-3表达的影响。结果:ROZ可呈剂量-5-4依赖性抑制MCF-7细胞的生长及集落形成。ROZ浓度为610M和310M时则G1期细胞数明显增加,S期相应减少。Hoechst33342染色经ROZ处理的肿瘤细胞染色质呈颗粒
3、状,且有凋亡小体出现。FCM检测结果显示,ROZ作用72h凋亡细胞数达22.05%。Westernblot提示ROZ可抑制Bcl-2表达,促进Caspase3表达。结论:ROZ在体外可抑制MCF-7细胞的增殖并诱导其凋亡,这可能与其抑制Bcl-2表达、促进caspase3表达有关。提示ROZ有望成为乳腺癌治疗药或肿瘤治疗的辅助用药,PPAR有潜力成为肿瘤治疗的新靶点。关键词:氧化酶体激活物增殖受体(PPAR);罗格列酮;生长抑制;凋亡StudyonPeroxisomeProliferator-
4、activatedReceptor-ActivationinInhibitingTumorGrowthandInducingApoptosisinBreastCancer11121LUHai-bo,ZHANGQing-yuan,ZHOUJian-hua,WANGYing,LUHai-ling1Departmentofoncology,theAffiliatedTumorHospitalofHarbinMedicalUniversity,Harbin150040,Heilongjiang,Chin
5、a2Departmentoflaboratory,theAffiliatedTumorHospitalofHarbinMedicalUniversity,Harbin150040,Heilongjiang,ChinaABSTRACTObjective:Toobservetheeffectsofrosiglitazone(ROZ),aperoxisomeproliferator-activatedreceptor-activation,intheinhibitionoftumorgrowthand
6、inducementapoptosisinbreastcancerinvitro.Methods:MTTwasusedtodetecthowROZinhibitedthegrowthofMCF-7,observingROZhowtoinfluencethecolonyformationofMCF-7bycolonyformationtest.AfterdifferentconcentrationofROZfor72hours,themorphologicchangeofMCF-7wasseenby
7、Hoechst33342dyeing;theapoptosispercentageandcellcyclechangeweredetectedbyFCM;theeffectsofROZintheexpressionofBcl-2andCaspase-3ofMCF-7wereevaluatedbyWesternBlotting.Results:UsingROZtotreatbreastcancer,withadose-dependence,couldinhibitcellgrowthandcolon
8、yformationofMCF-7.ThenumberofcellsinG1phasein--5-4creasedandthenumberofcellsinSphasedecreasedwhentheconcentrationofROZwas610Mand310M.ThroughHoechst33342dye-ing,thereweregranulochromatinandapoptoticbodyintumorcellsafterbeingtreatedwithROZfor7