Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines

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1、Biomedicine&Pharmacotherapy74(2015)49–56AvailableonlineatScienceDirectwww.sciencedirect.comOriginalArticleInhibitionofproteinglycosylationreversestheMDRphenotypeofcancercelllinesa,*,aaa,bKarolinaWojtowiczRadosławJanuchowski,MichałNowicki,MaciejZabelaDepartmentofHis

2、tologyandEmbryology,PoznanUniversityofMedicalSciences,60-781Poznan,PolandbDepartmentofHistologyandEmbryology,WroclawMedicalUniversity,50-368Wroclaw,PolandARTICLEINFOABSTRACTArticlehistory:Background:Multidrugresistanceproteinsareoneofthemostimportantfactorsthatcaus

3、eReceived12June2015chemotherapyresistance,whichinturnreducestherapeuticefficacyandsurvivalforcancerpatients.Accepted9July2015Tunicamycinisoneofthemostwell-knowninhibitorsofN-glycosylationandisconsideredapowerfuladjunctthatcanincreasetheeffectivenessofmanydrugs.Tunic

4、amycinblocksthefirststepofP-gpKeywords:(glycoproteinP)andBCRP(breastcancerresistanceprotein)N-glycosylation,whichisaveryimportantMultidrugresistancemodificationTunicamycinfortheactivityandcellularlocalisationoftheseproteins.Methods:Theeffectsoftunicamycinonovarianand

5、colorectalcancercellswereexaminedinmultipleChemotherapycelllines.TheprimaryovariancancercelllineW1andtheestablishedovariancancercelllineA2780GlycoproteinPBCRPwerecomparedagainsttheirdrug-resistantderivativesW1TR/W1PR(TR:topotecanresistant;PR:paclitaxelresistant)and

6、A2780T1(topotecanresistant),respectively.WealsocomparedthecolorectalcancercelllineLoVoagainstitsdoxorubicin-resistantderivativeLoVo/Dx.CellviabilitywasdeterminedbytheMTTassay.TheglycopeptidesweresubjectedtodeglycosylationusingtheendoglycosidasePNGaseF.A2780T1,LoVo/

7、DxandW1PRcellsweretreatedwiththeproteindegradationinhibitorsMG132andBMA.Proteinexpressionwasdetectedbywesternblotandimmunocytochemistry.Results:Inthisstudy,weshowedviatheMTTassaythattunicamycinsignificantlydecreasedtheviabilityofcancercelllinesthatwereco-treatedwith

8、achemotherapeuticdrug.Westernblotanalysisshowedthat,inLoVo/DxandW1PRcells,tunicamycintreatmentresultedintheexpressionofa70kDaP-gpproteininsteadof