sensitivity of leukemic cell line hl-60 to combination of neferine and arsenic

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1、SENSITIVITYOFLEUKEMICCELLLINEHL-60TOCOMBINATIONOFNEFERINEANDARSENICChineseJournalofCancerResearch18{3):183—187,2006183SENSITIVITYoFLEUKEMICCELLLINEHL一60ToCoMBINATIoNoFNEFERINEANDARSENICLIUGe.xiu刘革修

2、c,ZHANGYuan张洹,HEDong-mei何冬梅InstituteofHematology,Jin

3、anUniversityMedicalCollege,Guangzhou510632CLCnumber:R733.7Documentcode:AArticleID:1000-9604(2006)03-0183-05ABSTRACTObjective:Todeterminewhetherneferine(Nef)enhancesthesensitivityofhumanmyeloidleukemiaHL一60celIstoarsenictrioxide(ATO).Methods:Apoptosis

4、wasdetectedbyDNAelectrophoresis.Giemsastainingwasusedtoobservetheapoptoticcellsundermicroscope.Theapoptoticratesofcellswereanalyzedusingflowcytometry.TheinhibitoryratesofcellgrowthwereassayedbyMTT,andtheexpressionofP—gpwasdeterminedbyflowcytometry.Re

5、sults:LowdosesofAT0(1.0txmol/L)onlypartiallyinhibitorypercentageofcellgrowthat72hwas(9.92~3.03)%rP>0.05,vscontro1).Thecombinationof1.0txmol/LATOwith2.01ampl/LNefinhibited(45.27~4.93)%ofce11growth,andinducedapoptosisinleukemiccellsmoresignificantly

6、thanwitherAT0orNefontheirown(P<0.01).Moreover,AT0-inducedexpressionofP—gpinleukemiccellswasinhibitedsignificantlybyNef.Conclusion:TheseresultsindicatethatNefsignificantlyincreasessensitivityofleukemicceIlstoATO,whichmightbeassociatedwithinhibitory

7、expressionofP—gpgene.Combineduseofthetwoagentscouldbeanovelandattractivestrategyinleukemiatreatment.Keywords:Neferine;Apoptosis;Arsenictrioxide;LeukemiaArsenictrioxide(ATO)hasbeenusedinthetreatmentofacutepromyelocyticleukemia,withahighrateofcompleter

8、emission【.However.inherentoracquiredresistancetocytotoxicdrug-inducedapoptosisisamajorconcerninthetleatmentofmanyleukemias.includingacutemyeloidleukemia(AML).Inaddition.AT0ispoisonous,andhasdeleteriouseffectsonliver,kidneyandotherorgansproportionalto

9、thedose【.Useofthisdrugmightbemadesaferandmoreemcient.anditstherapeuticeffectsmightbeenhancedbyanagentthatactssynergisticallywithit.ThepredominantcauseofmultidrugresistancefMDR)oftumorcellsistheoverexpressionanddrugtransportactivityofP-glycoprotein(P-