突變型IκBα對HL-60細胞凋亡和分化作用的初步研究.pdf

1、中南大學碩士學位論文突變型IκBα對HL60細胞凋亡和分化作用的初步研究姓名：高彩霞申請學位級別：碩士專業(yè)：內(nèi)科學（血液病學）指導教師：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