单纯疱疹病毒胸苷激酶／更昔洛韦系统联合化疗药物治疗前列腺癌

430022HSV-TKGCVHRPCPC-3mHSV-TKPC-3mMTTGCV10μmolLCDDP10μmolLVP-1610μmolLVCR135nmolLMTX5nmolL5-5-Fu1μmolL100μmolLGCVPC-3mFCMGCV5-FuHSV-TKGCVVP-16VCR5-FuPC-3mCDDPMTXFCMGCV5-Fu72h36.38%35.51%33.05%28.87%HSV-TKGCVPCaCooperativetherapeuticeffectsofherpessiLplexvirusthyLidinekinasegeneganciclovirsysteLandcheLotherapeuticagentsonprostatecancerinvitroXINGYi-feiXIAOYa-junZENGFu-qingetal.DepartmentofUrologyUnionHospitalTongjiMedicalCollegeHuazhongUniversityofSci-enceandTechnologyWuhan430022ChinaAbstractObjectiveToinvestigatethekillingeffectsofherpessimplexvirusthymidinekinasegeneganciclovirHSV-TKGCVapproachbytheadditionofseveralcommonlyclinicalchemotherapeu-ticagentsonhormonerefractoryprostatecancerHRPCcellsPC-3m.MethodsAftertransferringoftheHSV-TKgeneintoPC-3mcellsthekillingeffectofGCV10μmolLcisplatinCDDP10μmolLetoposideVP-1610μmolLvincristineVCR135nmolLmethotrexateMTX5nmolL5-fluorouracil5-Fu1μmolLandsuramin100μmolLonPC-3mcellswasevaluatedbytrypanblueexclusionassayandMTTassayrespectively.AdditionallythecooperativeeffectofHSV-TKGCVsystemcombinedwiththeaboveagentsonthetargetcancercellswasdeterminedbyMTT.Furthermoreapopto-sisandnecrosisinducedbyGCVplus5-FuorsuraminwasanalyzedbyflowcytometryFCM.ResultsCombinationofHSV-TKGCVsystemwithVP-16VCR5-FuorsuramincouldenhancecellularkillingeffectbutwithCDDPresultedinareducedoneandwithMTXbroughtanapproximateone.FCMmani-festedthatsynergisticuseofGCVand5-Fuorsuraminresultedinaratherlargeproportionofapoptosisandnecrosis.Theindexofapoptosiswas36.38%and35.51%andtheproportionofnecrosiswas33.05%and28.87%respectively.ConclusionHSV-TKCGVapproachbyadditionofcertainclinicalavailablechemotherapeuticdrugsbringsonstatisticallysignificantenhancedcellularkillingeffectoversin-gle-agenttreatment.KeywordsProstaticneoplasmsThymidinekinasegeneGanciclovirChemotherapyGenetherapyHSV-TKGCV1PCaHSV-TKGCVPCa1.HSV-TKEpstein-BarrEBpDR2-TKDosperReagentBoehringerMannheinGCVSigmaCDDPVP-165-5-Fu76312005112211ChinJExpSurgNovember2005Vol22No.11MTXVCRPIMTTDM-SOSigma2.PC-3mPCa3.DosperReagent4.TKPC-3mTK+243*10472hGCV10μmolL5-Fu1μmolL100μmolLVP-1610μmolLVCR135nmolLMTX5nmolLCDDP10μmolLGCV5.TK+961*1043GCV72hMTTA4906.FCMHSV-TKGCV5-FuFCM72hPIDNA7.t1.GCVCDDPMTXPC-3mCDDPMTX2.A490GCVA1.044+0.090GCVVP-16VCR5-FusuraminA0.622+0.1010.673+0.0770.380+0.0490.428+0.069P0.05~0.001CDDPA1.217+0.040P0.05MTX0.914+0.106P0.05HSV-TKGCV5-FusuraminVP-16VCRPCaCDDP3.DNAGCV5-Fu72hPC-3m33.05%28.87%36.38%35.51%GCV5-Fu13.54%12.45%9.41%19.05%21.70%18.26%HSV-TKGCV2HSV-TKGCV5-FuPCaGCV5-FuVP16VCRPC-3mGCV5-Fu72h75.37+1.99%61.87+3.61%70.70+3.32%29.97+1.72%31.60+2.80MTXCDDPHSV-TKGCVPCa3GCV5-FuPC-3mFCM72hGCVTK5-FuTSGCVHSV-TKGCVGCV-TP5-FuHSV-TKGCVDNAHSV-TKGCVVP-16VCRDNACD-DPDNAGCV-TPDNAHSV-TKGCV1.HSV-TKGCV.200217680-682.2..2003201023-1024.3..200320107-108.2004-12-0986312005112211ChinJExpSurgNovember2005Vol22No.11