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ID:33216833
大小:3.91 MB
页数:37页
时间:2019-02-22
《硼替佐米对急性髓性白血病细胞凋亡及sall4基因和wnt信号通路的影响》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、重庆医科大学硕士学位论文硼替佐米对急性髓性白血病细胞凋亡及SALL4基因和Wnt信号通路的影响姓名:傅雷华申请学位级别:硕士专业:内科学指导教师:陈林201205重庆医科大学硕士研究生学位论文硼替佐米对急性髓性白血病细胞凋亡及SALL4基因和Wnt信号通路的影响摘要目的:探讨硼替佐米对急性早幼粒细胞白血病NB4细胞株和急性红白血病TFl细胞株的凋亡诱导作用及其对SALL4基因和Wnt/p-catenin信号通路下游靶基因C-myc、CCDNl的影响。方法:MTT法检测细胞增殖情况;流式细胞术检测细胞凋亡率;免疫细胞化学检测SALL4蛋白表达;WesternBlot检测SA
2、LL4蛋白的表达情况。荧光定量PCR检测SALL4、C.myc、CCNDl基因表达情况。结果:硼替佐米抑制两种细胞的增殖,呈时间和计量依赖性。NB4和TFl细胞48hIC50分为23.97nmol/L和25.36nmol/L。硼替佐米诱导两种细胞凋亡作用呈剂量依赖性。经30、50nmol/L浓度硼替佐米处理后24h后,NB4细胞的凋亡率分别为(27.75+1.77)%和(40.45+12.80)%,与对照组(4.65+3.18)%相比差异具有统计学意义(氏O.05);50nmol/L浓度硼替佐米处理后24h后,TFl细胞的凋亡率为(64.60+1.31)%,与对照组(16
3、.15+2.90)%相比,差异具有显著性(尸4、/[3-catenin信号通路下游靶基因C-myc、CCNDl的抑制在硼替佐米诱导NB4、TFl细胞凋亡的过程可能起重要作用。关键词:硼替佐米,SALL4基因,Wnt信号通路,急性髓性白血病重庆医科大学硕士研究生学位论文INFLUENCEoFBORTEZOMIBoNACUTEMYELoGENOUSLEUKEMIACELLSAPoPTOSISANDITSEFFECTSoNSALL4GENEANDWNTSIGNALINGPATHWAYABSTRACTObjective:ToinvestigateBortezomib-inducedapoptosisofacutemyeloge5、nousleukemiacelllinesNB4,TF1anditseffectonexpressionsofSALL4geneandtargetgenesofWnt/13一cateninpathway.Methods:ProliferationswereanalyzedbyMTTassay.Apoptosisratesweredetectedbyflowcytometer.SALL4proteinwasdetectedbyimmtmocytochemistrySALL4proteinsintwocelllinesweredetectedbyWesternBlot.The6、expressionsofSALL4.C—mycandCCND1genesintwocelllinesweredetectedbyReal—timePCR.Results:Bortezomibinhibitedtheproliferationsoftwocelllinesinatime-and-doesdependingmanner.NB4andTFlcells’48hIC50were23.97nmol/Land25.36nmol/L.Bortezomibinducedtwocelllinesapoptosisinadoes-dependingmanner.Afterce7、llsweretreatedbyBortezolnibfor24h,theapoptosisratesofNB4cellsin30nmol/Land50nmol/Lgroupswere(27.75±1.77)%and(40.45土12.80)%respectively,whichhadasignificantdifferenceincomparingwiththatofcontrolgroup(4.65i3.18)%(尸
4、/[3-catenin信号通路下游靶基因C-myc、CCNDl的抑制在硼替佐米诱导NB4、TFl细胞凋亡的过程可能起重要作用。关键词:硼替佐米,SALL4基因,Wnt信号通路,急性髓性白血病重庆医科大学硕士研究生学位论文INFLUENCEoFBORTEZOMIBoNACUTEMYELoGENOUSLEUKEMIACELLSAPoPTOSISANDITSEFFECTSoNSALL4GENEANDWNTSIGNALINGPATHWAYABSTRACTObjective:ToinvestigateBortezomib-inducedapoptosisofacutemyeloge
5、nousleukemiacelllinesNB4,TF1anditseffectonexpressionsofSALL4geneandtargetgenesofWnt/13一cateninpathway.Methods:ProliferationswereanalyzedbyMTTassay.Apoptosisratesweredetectedbyflowcytometer.SALL4proteinwasdetectedbyimmtmocytochemistrySALL4proteinsintwocelllinesweredetectedbyWesternBlot.The
6、expressionsofSALL4.C—mycandCCND1genesintwocelllinesweredetectedbyReal—timePCR.Results:Bortezomibinhibitedtheproliferationsoftwocelllinesinatime-and-doesdependingmanner.NB4andTFlcells’48hIC50were23.97nmol/Land25.36nmol/L.Bortezomibinducedtwocelllinesapoptosisinadoes-dependingmanner.Afterce
7、llsweretreatedbyBortezolnibfor24h,theapoptosisratesofNB4cellsin30nmol/Land50nmol/Lgroupswere(27.75±1.77)%and(40.45土12.80)%respectively,whichhadasignificantdifferenceincomparingwiththatofcontrolgroup(4.65i3.18)%(尸
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