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《Chinese Journal of Obstetrics And Gynecology》 1996-02
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ExperimentalStudyontheMechanismofCisplatinResistanceandItsReversioninHumanOvarianCancer

LiangZhengdong,BianDuhong.1stAffiliatedHospital,ChongqingMedicalUniversity,Chongqing630042  
Objective:Toexplorethemechanismofcisplatinresistanceanditsreversioninhumanovariancancer.Methods:Axenograftedcisplatinresistantmicemodelofhumanovariancancer,SKOV3/cp,wasdevelopedbythemicroencapsulatedtechnique.Themultiplechangesofbio-chemicalmarkersinthemodelweredetermined,andvariousmodulatorsforreversionweretested.Results:IntracelularplatinumacumulationinSKOV3was5.1times,Pt-DNAadducts2.4timesandinterstrandcroslinkofDNA(ISC)4.8timesofthoseincisplatin-resistantcelline,SKOV3/cp.ThesechangesinSKOV3/cpcouldnotbereversedbyverapamil.AmphotercinB(AmB)andNovobiocin(NVB)couldraisetheconcentrationsofplatinumandPt-DNAadductsinSKOV3/cp,resultingincompleteorpartialreversionofcisplatin-resistanceofSKOV3/cp.Therewerenodiferencesintotalglutathione(GSH)levelandinsensitivitytoCdCl2betweenSKOV3andSKOV3/cp.Conclusions:ItissuggestedthattheprimaryfactorcausingSKOV3/cpresistancetocisplatinisthereductionofintracelularplatinumaccumulationandtheaugmentationoftheabilitytoremovePt-DNAadducts.Theresistanceisnotconsideredtobeassociatedwiththemultidrugresistant,GSH,metalothioneinsystems.AmBandNVBcanovercomecisplatinresistanceofSKOV3/cpinvitroandinvivo.
【CateGory Index】: R737.31
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