突變型IκBα對(duì)HL-60細(xì)胞凋亡和分化作用的初步研究.pdf

1、中南大學(xué)碩士學(xué)位論文突變型IκBα對(duì)HL60細(xì)胞凋亡和分化作用的初步研究姓名：高彩霞申請(qǐng)學(xué)位級(jí)別：碩士專業(yè)：內(nèi)科學(xué)（血液病學(xué)）指導(dǎo)教師：王光平20070501ABSTACTNFkappaB(NF—rB)transcriptionfactoriSthekeYregulatorofgeneexpressionandplaysacriticalroleininflammatoryreactionimmuneresponse，celldiffe

2、rentiationandapoptosisRecently，somestudiesshowthatNFrBisactivatedpersistentlyinmanyhumantumorsandpromotethetumorcellsresistancetoapoptosisinducedbyradiotherapyandchemicaldrugsBycontrastinhibitionofNF—rBcaninducetheapopto

3、sisoftumorcellsandenhancetheeytotoxiceffectofthechemicaldrugsMeanwhile，studiesdemonstratedthatNFrBisactivatedinacutemyeloidleukemia(AML)primarycellsandthecelllinessuchasHL一60ceilsAtpresentthestudiesoninhibitorsofNF—rBmai

4、nlyconsistoffouraspects，ie，(1)Olddrug，newtricks，suchasglucocorticoid、thalidomide(2)NewinhibitorofNFrB(3)RNAi(RNAinterfering，RNAi)technology(4)MutantIrBaAgreatnumberofstudieshaveindicatedthatallofthesemethodsCanUSetoinhib

5、itionofNFrB。andinduceapoptosisofthetunlorcellsButitisalsoaccompaniedwithsomeproblemsForexample，mostoftheconventionaldrugsandnewinhibitorsofNF一●cBdon’tspecificallyblocktheactivityofNF—rB，andlongtermuseofthemCanbringaboutt

6、oxiceffectAlthoughinhibitionofNFrBthroughs遼姒iscarriedoutitiSstillalongtimetogointoclinicaltherapyFurthermore，somestudiesshowthatsite—specificmutantI’cBCaninducetheapoptosisandinhibittheproliferationofthetumorcellsHowever

7、Therearefewarticlesthatreportthedeletionmutant11cBcanaffecttheapoptosisanddifferentiationofHL60cellobjeetiveANterminalaminoaciddeletionformofIrBaWastransfectedintoHL60celltoexploretheeffectsofthemutantI’①aontheapoptosisa

8、nddifferentiationofthecellsinthisstudyMethodTheplasmidDNAoftherecombinantpCLXIr。Ba△NwastransfefredintoHL60cellsbycathodolyteliposomeThencellswereharvestedafterIransfection48hand72hrespectively111etranscriptofIgSainHL一60c