抑制卵巢癌细胞株ALDH1A1活性可降低

　　年9月，爱思唯尔旗下《国际生物化学与细胞生物学杂志》正式发表波兰波兹南医科大学、弗罗茨瓦夫医科大学的研究报告，发现对紫杉醇和托泊替康耐药的卵巢癌细胞株可见醛脱氢酶1A1（ALDH1A1）高表达，抑制卵巢癌细胞株ALDH1A1活性可降低药物转运蛋白表达并减少托泊替康等化疗药物的耐药性。

IntJBiochemCellBiol.Sep;78(1):-59.

InhibitionofALDH1A1activitydecreasesexpressionofdrugtransportersandreduceschemotherapyresistanceinovariancancercelllines.

JanuchowskiR,WojtowiczK,SterzyńskaK,SosińskaP,AndrzejewskaM,ZawieruchaP,NowickiM,ZabelM.

PoznańUniversityofMedicalSciences,Poland;WroclawMedicalUniversity,Poland.

Highlights

HighexpressionofALDH1A1wasobservedinpaclitaxelandtopotecan-resistantcancercelllines.

PretreatmentwithATRAandDEABreducedchemotherapyresistanceininvestigatedcelllines.

ATRAtreatmentledtodownregulationofALDH1A1,P-gpandBCRPproteins.

DEABtreatmentledtodownregulationofP-gpandBCRPproteins.

Thehighmortalityofovariancancerpatientsresultsfromthefailureoftreatmentcausedbytheinherentoracquiredchemotherapydrugresistance.ItwasreportedthatoverexpressionofaldehydedehydrogenaseA1(ALDH1A1)incancercellscanberesponsibleforthedevelopmentofdrugresistance.ToaddthehighexpressionofthedrugtransporterproteinstheALDHA1isconsideredasamoleculartargetincancertherapy.Therefore,weanalyseddrug-resistantovariancancercelllinesaccordingtoALDHA1expressionandtheassociationwithdrugresistance.TheexpressionofALDH1A1,P-glycoprotein(P-gp)orbreastcancerresistanceprotein(BCRP)wasdeterminedusingamicroarrayandconfirmedbyQ-PCR,westernblotandfluorescenceanalysis.ALDH1A1activitywasdeterminedusinganAldefluorassay.Theimpactofall-transretinoicacid(ATRA)anddiethylaminobenzaldehyde(DEAB)onchemotherapyresistancewasassessedbytheMTTchemosensitivityassay.ThemostabundantexpressionofALDH1A1wasnotedinpaclitaxel-andtopotecan-resistantcelllineswheretwopopulationsofALDH-positiveandALDH-negativecellscouldbeobserved.ThosecelllinesalsorevealedtheoverexpressionofP-gpandBCRPrespectively,andwereabletoformspheresinnon-adherentconditions.Pre-treatmentwithATRAandDEABreducedchemotherapyresistanceinbothcelllines.ATRAtreatmentledtodownregulationoftheALDH1A1,P-gpandBCRPproteins.DEABtreatmentledtodownregulationoftheP-gpproteinandBCRPtranscriptandprotein.OurresultsindicatethatALDH1A1-positivecancercellscanberesponsiblefordrugresistancedevelopmentinovariancancer.DevelopingmorespecificALDH1A1inhibitorscanincreasechemotherapyeffectivenessinovariancancer.

KEYWORDS:aldehydedehydrogenase1A1;anticancertherapy;drugresistance;drugtransporters;ovariancancerstemcells

PMID:

PII:S-(16)-1

DOI:10./j.biocel..07.

国际生物化学与细胞生物学杂志

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