Adenylate Kinase 3 Sensitizes Cells to Cigarette Smoke Condensate Vapor Induced Cisplatin Resistance 英文参考文献.docVIP

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Adenylate Kinase 3 Sensitizes Cells to Cigarette Smoke Condensate Vapor Induced Cisplatin Resistance 英文参考文献.doc

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Adenylate Kinase 3 Sensitizes Cells to Cigarette Smoke Condensate Vapor Induced Cisplatin Resistance 英文参考文献

AdenylateKinase3SensitizesCellstoCigaretteSmoke CondensateVaporInducedCisplatinResistance XiaofeiChang,RajaniRavi,VuiPham,AtulBedi,AditiChatterjee*,DavidSidransky* DepartmentofOtolaryngology-HeadandNeckSurgery,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract Background: The major established etiologic risk factor for bladder cancer is cigarette smoking and one of the major antineoplasticagentsusedforthetreatmentofadvancedbladdercanceriscisplatin.Anumberofreportshavesuggested thatcancerpatientswhosmokewhilereceivingtreatmenthavelowerratesofresponseanddecreasedefficacyofcancer therapies. Methodology/PrincipalFindings:Inthisstudy,weinvestigatedtheeffectofcigarettesmokecondensate(CSC)vaporon cisplatintoxicityinurothelialcelllinesSV-HUC-1andSCaBERcells.WeshowedthatchronicexposuretoCSCvaporinduced cisplatinresistanceinbothcelllines.Inaddition,wefoundthattheexpressionofmitochondrial-residentproteinadenylate kinase-3(AK3)isdecreasedbyCSCvapor.WefurtherobservedthatchronicCSCvapor-exposedcellsdisplayeddecreased cellularsensitivitytocisplatin,decreasedmitochondrialmembranepotential(DYm)andincreasedbasalcellularROSlevels compared to unexposed cells. Re-expression of AK3 in CSC vapor-exposed cells restored cellular sensitivity to cisplatin. Finally,CSCvaporincreasedthegrowthofthetumorsandalsocurtailtheresponseoftumorcellstocisplatinchemotherapy invivo. Conclusions/Significance:ThecurrentstudyprovidesevidencethatchronicCSCvaporexposureaffectsAK3expressionand rendersthecellsresistanttocisplatin. Citation:ChangX,RaviR,PhamV,BediA,ChatterjeeA,etal.(2011)AdenylateKinase3SensitizesCellstoCigaretteSmokeCondensateVaporInducedCisplatin Resistance.PLoSONE6(6):e20806.doi:10.1371/journal.pone.0020806 Editor:AndreiL.Gartel,UniversityofIllinoisatChicago,UnitedStatesofAmerica ReceivedNovember5,2010;AcceptedMay12,2011;PublishedJune15,2011 Thisisanopen-accessarticle,freeofallcopyright,andmaybefreelyreproduced,distributed,transmitted,modified,builtupon,or