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《替莫唑胺聯(lián)合二甲雙胍對(duì)膠質(zhì)瘤干細(xì)胞的清除作用及其機(jī)制_余志云》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、第41卷第2期吉林大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)Vol.41No.22015年3月JournalofJilinUniversity(MedicineEdition)Mar.2015321[文章編號(hào)]1671-587Ⅹ(2015)02-0321-06DOI:10.13481/j.1671-587x.20150223替莫唑胺聯(lián)合二甲雙胍對(duì)膠質(zhì)瘤干細(xì)胞的清除作用及其機(jī)制余志云1,李蘊(yùn)潛1,陳勇1,趙麗艷2,劉煥兵1,王楠1,王斌1,陳云照1,趙剛1(1.吉林大學(xué)第一醫(yī)院神經(jīng)外科,吉林長(zhǎng)春130021;2.吉林大學(xué)第一醫(yī)院檢驗(yàn)科,吉林長(zhǎng)春130
2、021)[摘要]目的:探討替莫唑胺(TMZ)聯(lián)合二甲雙胍(MET)對(duì)體外膠質(zhì)瘤干細(xì)胞(GSCs)的清除作用,探討其作用機(jī)制。方法:神經(jīng)干細(xì)胞培養(yǎng)基培養(yǎng)人膠質(zhì)瘤U87細(xì)胞,免疫熒光法鑒定GSCs。收集GSCs,以對(duì)照液、不同濃度TMZ、MET和TMZ+MET作用細(xì)胞,分為對(duì)照組、TMZ組、MET組和TMZ+MET組。顯微鏡下計(jì)數(shù)各組二次神經(jīng)球的數(shù)量;CCK-8法檢測(cè)各組GSCs增殖抑制率;流式細(xì)胞術(shù)和Annexin-PI雙染流式細(xì)胞術(shù)檢測(cè)GSCs各細(xì)胞周期百分比和凋亡率。結(jié)果:與對(duì)照組比較,TMZ+MET組二次神經(jīng)球數(shù)量以濃度
3、依賴(lài)的方式減少;與TMZ和MET組比較,TMZ+EMT組二次神經(jīng)球數(shù)量明顯減少(P<0.01)。與對(duì)照組比較,TMZ和MET組GSCs增殖抑制率升高;TMZ+MET組GSCs增殖抑制率高于TMZ或MET組,聯(lián)合指數(shù)(CI)小于1。流式細(xì)胞術(shù),與TMZ和MET組比較,TMZ+MET組G2/M期GSCs百分比明顯升高(P<0.05);TMZ+MET組GSCs凋亡率明顯高于TMZ和MET組(P<0.05)。結(jié)論:TMZ聯(lián)合MET在體外能抑制GSCs的連續(xù)自我更新能力并清除GSCs,其機(jī)制可能與阻滯GSCs細(xì)胞周期進(jìn)展和誘導(dǎo)細(xì)胞凋亡
4、有關(guān)聯(lián)。[關(guān)鍵詞]替莫唑胺;二甲雙胍;膠質(zhì)瘤干細(xì)胞;自我更新[中圖分類(lèi)號(hào)]R730.264[文獻(xiàn)標(biāo)志碼]AEliminationoftemozolomideincombinationwithmetforminongliomastemcellsanditsmechanism1,LIYunqian1,CHENYong1,ZHAOLiyan2,LIUHuanbing1,WANGNan1,YUZhiyun1,CHENYunzhao1,ZHAOGang1WANGBin(1.DepartmentofNeurosurgery,FirstH
5、ospital,JilinUniversity,Changchun130021,China;2.DepartmentofClinicalLaboratory,FirstHospital,JilinUniversity,Changchun130021,China)Abstract:ObjectiveToexploretheeffectoftemozolomide(TMZ)incombinationwithmetformin(MET)ontheeliminationofglioblastomastemcells(GSCs)inv
6、itro,andtoclarifythemechanism.MethodsThehumangliomaU87cellswereculturedintheneuralstemcellmedium,andtheGSCswereidentifiedbyimmunofluorescencemethods;theGSCswereselectedandweretreatedwithcontrolsolution(controlgroup),differentconcentrationsofTMZ(TMZgroup)andMET(METg
7、roup)orTMZcombinedwithMET(TMZ+METgroup).Thenumberofsecondaryneurosphereswerecountedundermicroscope,andtheinhibitoryrateofproliferationofGSCswasdetectedbyCCK-8assay;flowcytometryandAnnexinⅤandPIstainingflowcytometrywereusedtodetectthepercentageofcellcycleandtheapopt
8、oticrateofGSCs,respectively.ResultsComparedwithcontrolgroup,thenumberofsecondaryneurospheresinTMZ+METgroupwassignificantlydecreasedinaconcentrati