Na-,2-SeO-,3-誘導人急性早幼粒白血病NB4細胞凋亡過程中細胞周期的改變及其機制研究.pdf

1、中國協(xié)和醫(yī)科大學碩士學位論文NaSeO誘導人急性早幼粒白血病NB4細胞凋亡過程中細胞周期的改變及其機制研究姓名：華方圓申請學位級別：碩士專業(yè)：生物化學與分子生物學指導教師：許彩民20060501中蹦悱和醫(yī)科大學碩士學位論文AbstractSodi哪selenileatce蹦nconcen缸lnonscouldi11hibitl1egfowtllofhumanAPL(acmepromyelocytic1cukeIIlia)一derived

2、NB4celIs，柏dinducetyplcalcell印optoslsCeIIgroⅥ曲a11dproli南raⅡonaretheresuItofceIlcyclepro釅essio皿Ⅵ，hichis呻dernghrregulationbythecellcyclemachmer弘Thus，meinhmitorye伍∞tofsodi啪seleni把ont11e筍owtllofNB4ceIIsmusthave血v0Ivedthedysre

3、guIationofceIlcycIepmgressionE1ucidanngthee位ctofsodi眥sclcIlitconthecellcycleprogressionofNB4cells鋤dtherelevampathway’wilIpotennyaddinsightiIlto【henlech肌ismofsodiulnseleniteindl】cedNB4cellgrow吐linhibitionandapoptosis，t11u

4、spr0Vidingnewb粘isforprobi“g仕1。rationalilyoftreati“gleukem訌In血istIesis，thedoscand廿mede口endeminbibhorvefrectofsodiluIIseleniteontllegfowtll鋤dpmlifbmtionofNB4cellswasconfimledTtwaSals0sh0、Ⅳntll砒sodi啪sclcnjtcatcertainconcemr

5、atjonsortreaⅡnemf昕certaintimelen垂hscouldsigllificalltIycI幽gethece兒cycJedisⅡib面0nprofileofNB4cellsFu九Ilerexperime力ts、vi山syncIl王ollizedceJlsdemons№tedth砒cdlssynchrDnizedatGl／SphaseandSphascshowcdsignmcantSphaseblockageaner

6、sodiuInseknitett℃a鋤ent，andmattheonsetofcei王cycJeprofilcch如geshappenedmucheadiertllaIlasyIIchD工lizedcellsItwasa工sodiscoveredthat唧oⅡgasynchonizedNB4cells，DNAreplicationactivitiesweresligbtlypromotedimmediatclyaftersodiumsc

7、IeIlitetreamIent(witIlin6hrs)，wllileabovea廿eatmenttimeof12hrs，DNAsynthesiz“gactivmesofcellsbegantodisplays們nginhibitorye旋cts，wi血asi蛐丘cantpropomonofsphasecelIsceasingt0repIicateDNA，andcecyclepmgressioⅡwasblockedatSphaseBe

8、sides，sy‘lchmnizedNB4cellsexhbitedsodiumselenite—inducedapoptosismuchfa毗rthallasyncllronizcdcells，a11dcellssynchlonizedatSphasewereshowntobetllemostsensitiVetosodi哪selen沁inducedapoptosisWes劬blotanalysjswasadoptedt0a11aly

9、ze1hein釘uenceofsodjumse】eniteont11elevelsofscveralcrucialcellcycIepfoteills，瑚melycycHnD3，CDK4，cyclinE，CDK2，cyclinA，CDKl，p15，andp27nwasdiscoveredthatthclevdand加de盯localiZa們onofthese口mteinswere趕rectedbysodi啪seleⅡitetreatme

10、nttodi飪hentextemscombinedwimdataf如mjmmunoprecipjtationstudies，these冊ult8pfobablyme趴tthaI廿leactiVitiesof山esecellcycleprotcmswere鋤ong血etargetsofsodiumseleIlite廿leactiVitiesofthesecellcycleprotemswere鋤ong血etargetsofsodiumse