Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth 英文参考文献.docVIP

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Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth 英文参考文献.doc

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Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth 英文参考文献

GapJunctionEnhancerIncreasesEfficacyofCisplatinto AttenuateMammaryTumorGrowth StephanieN.Shishido,ThuA.Nguyen* DepartmentsofDiagnosticMedicine/Pathobiology,KansasStateUniversity,Manhattan,Kansas,UnitedStatesofAmerica Abstract Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines(PQs)actsasgapjunctionenhancer,abilitytoincreasethegapjunctionalintercellularcommunication,inbreast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showinganincreaseinefficacyofantineoplasticdrugsviatheenhancementofgapjunctions.Micewereimplantedwith estradiol-17?(1.7mg/pellet)beforetheinjectionof16107T47Dbreastcancercellssubcutaneouslyintotheinguinalregion ofmammaryfatpad.AnimalsweretreatedintraperitoneallywithDMSO(control),cisplatin(3.5mg/kg),PQ(25mg/kg),or acombiningtreatmentofcisplatinandPQ.Cisplatinalonedecreasedmammarytumorgrowthby85%whilecombinational treatmentofcisplatinandPQ1orPQ7showedanadditionalreductionof77%and22%oftumorgrowthafter7treatments atevery2days,respectively.Histologicalresultsshowedasignificantincreaseofgapjunctionproteins,Cx43andCx26,in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinationaltreatment(PQandcisplatin)wasseencomparedtocisplatinalone.Wehaveshowedforthefirsttimean increaseintheefficacyofantineoplasticdrugsthroughacombinationaltreatmentwithPQs,aspecificclassofgapjunction enhancers. Citation:ShishidoSN,NguyenTA(2012)GapJunctionEnhancerIncreasesEfficacyofCisplatintoAttenuateMammaryTumorGrowth.PLoSONE7(9):e44963. doi:10.1371/journal.pone.0044963 Editor:PranelaRameshwar,UniversityofMedicineandDentistryofNewJersey,UnitedStatesofAmerica ReceivedJuly6,2012;AcceptedAugust10,2012;PublishedSeptember13,2012 Copyright:?2012Shishido,Nguye