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1、第31卷第4期浙江大学学报(医学版)Vol31No42002年JOURNALOFZHEJIANGUNIVERSITY(MEDICALSCIENCES)2002乌苯美司对人白血病细胞生长抑制及其机制探讨何静松,林茂芳,麦文渊,钱文斌(浙江大学医学院附属第一医院,浙江杭州310003)[摘要]目的:研究国产氨肽酶N抑制剂乌苯美司(Ubenimex)对人白血病细胞的作用及其机理。方法:应用MTT比色法观察Ubenimex对细胞的生长抑制作用,光学显微镜观察细胞形态结构的改变,DNA凝胶电泳、DNA片段原位末端标记及流式细胞仪(FCM)检测,分析细胞凋亡。结果:
2、①Ubenimex明显抑制HL60细胞的生长,半数抑制浓度(IC50)为13.03Lgöml;而K562细胞的敏感性较差。其抑制作用均呈剂量效应关系。②典型的细胞形态改变,DNA片段化,DNA末端原位标记的检出及流式细胞仪结果,均证实Ubenimex能诱导白血病细胞的凋亡。③10LgömlUbenimex作用12h即可明显诱导HL60细胞DNA断裂,K562细胞的凋亡敏感性显著低于HL60细胞;两者凋亡率均呈剂量和时间依赖性,经Ubenimex处理后,HL60细胞出现G1期阻滞。结论:Ubenimex能抑制K562,HL60细胞生长,诱导细胞凋亡是其机制
3、之一。[关键词]乌苯美司ö药理学;HL60细胞;K562细胞;细胞凋亡[中图分类号]R733.7;R967[文献标识码]A[文章编号]100829292(2002)0420259206MechanismsofinhibitoryeffectofUbenimexonhumanleukemiccellsHEJing2song,LINMao2fang,MAIWen2yuan,etal(TheFirstAffiliatedHospital,CollegeofMedicalSciences,ZhejiangUniversity,Hangzhou310003,Chi
4、na)[Abstract]Objective:TostudythemechanismofinhibitoryeffectofUbenimexonhumanleukemiccells.Me-thods:K562andHL60cellsweretreatedwithUbenimexatdifferentconcentrations,andthegrowthinhibitionwasanalysedbyMTTassay.Cellapoptosiswasevaluatedbylightmicroscopy,agrosegelelectrophoresis,TUN
5、ELlabelingmethodandflowcytometry(FCM)assay.Results:①TreatmentwithUbenimexremarkablyin2hibitedthegrowthofHL60cells,theIC50ofUbenimexforHL60cellswas13.03Lgöml.ButK562cellswerelesssensitivethanHL60.UbenimexinhibitedthegrowthofHL60andK562cellsinadose2dependentmanner.②Apoptpsisofleuke
6、miccellswasinducedbyUbenimex,whichwasshownbythechangesinmorphology,DNAlad2FITCderonagrosegel,TUNELlabeling,typicalpeakbeforeG1phaseofcellcycleandthepositiveofAnnexinÍonthecellsmembranewithFCM.③UbenimexinducedapoptosisofK562andHL60cellsinadose2andtime2depen2dentmanner.④Thecellcycl
7、eanalysisbyFCMshowedthattheHL60cellswereblockedinG1phaseaftertreatedbyUbenimex.Conclution:UbenimexcanefficientlyinduceapoptosisofHL60andK562cells,thismaybeoneofthemechanismsforinhibitingeffectofUbenimexonleukemia.[Keywords]Ubenimexöpharmacol;HL60cells;K562cells;Apoptosis[JZhejian
8、gUniv(MedicalSci),2002,31(4):259-264.][2