sirna沉默htert基因对人胰腺癌的凋亡与耐药基因的影响

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1、EffectsofsilencingexpressionofhTERTbysiRNAontheapoptosisandresistancedrugsassociatedgenesofhumanpancreaticcancercellsinvitroDepartmentofGastroenterologyTheSecondAffiliatedHospital，SunYat—senUniversity,Guangzhou510120，China．M．D．candidate：ZhongYingqiangSupervisor：Pro

2、f．ZhuZhaohuaABSTRACTBACKGRoUNDPancreaticcancer(PC)isoneofcommonmalignanttumorsindigestivesystem，whichtheincidenceofPCisincreasingintheworld，andithasaddedtofourtimesfor2decadeinourcountry．Nowaday,oneofcausesofpooreffectofnon—surgicaltherapy,suchaschemotherapy,radiot

3、herapy,immunotherapyandendocrinotherapyonPC，ishigherexpressionsoftelomerase，anti—apoptosisgeneandresistencedruggeneinPCtissues．Lateseveralyears，thelevelofsynthetictherapeuticmodalsonPChasbeenadvancing，butthegreaterprogressaboutfavorablelongereffectandprognosishasno

4、toccurred．Withdeeplystudyofmolecularbiologyandoncologyassociatedsciences，thegenetherapyofPChasbeenanewertumor-therapeuticmodalthanthetraditionaltherapiessuchassurgicaloperation,radiotherapyandchemotherapy．HumantelomeraseiSconsistofthreesubunitsoftelomeraseRNA，telom

5、erasebindingpmteinandhumantelomerasereversetranscriptase(hTERT)，anditisresponsibleforadditionofTTAGGGrepeatstothetelomereendsofthechromosome，andmaintainningthestabletelomerelength．hTERTisaclosedcorrelationwithtelomeraseactivityinvivoorvitrocells，andalimitedfactorof

6、expressionoftelomeraseactivity．Therefore，toregulatetheexpressionofhTERThasbecomeamainmethodofregulatingtelomeraseactivity,andoneoftargetsofgenetherapyabouttelomerase．Recently,manystudieshaveindicatedthathTERThasnotonlytelomere—dependentfunctions，butalsotelomere-ind

7、ependentfunctions，thisisextratelomericfunctions，suchasenhancingtumorigenesis，anti—apoptosis，genomicstabilityandDNArepairfunction，regulatingtheexpressionofgenesthatcontrolcellgrowth．SotheextratelomericfunctionofhTERThasahotresearchfield．Cyciooxygenase-2(cox一2)geneis

8、associatedwithtumorcellproliferationandapoptosis．COX一2proteinisakeyenzymeinthecomersionofarachidonicacidtoprostaglandins．Therehasbeenunknownwheth