Thetherapeuticeffectofherpessimplexvirusthymidinekinase/ganciclovir(HSV-tk/GCV)systemonhepatocellularcarcinomawasstudiedinthisexperiment.Thetk-containingretroviralrecombinantswereusedtoinfecthepatomacells(BEL-7402)andthecellsweretreatedwithganciclovir(0-100μg/ml).TheresultsshowedthatHSV-tkgenecouldbeefficientlytransferredinvitrointohepatomacellsandstablyexpressed.Thegrowthpotentialofthetk-containingcellswassignificantlyinhibitedbyGCV(P<0.01)ascomparedtothenon-tk-containingcells.TheantitumoreffectofHSV-tk/GCVsystemwasalsoproducedexvivointk-containingtumorofnudemiceascharacterizedbyamarkeddecreaseintumorgrowthafterGCVtreatmentcontrarytoaprogressiveenlargementofnon-tk-containingtumors.Althoughthehistologicalexaminationdemonstratedthattheefficiencyofthegenetransferwaslessthan30%,thekillingeffectofHSV-tk/GCVsystemonhepatocellularcarcinomawasstillsignificantlygenerated.ThegropermechanismofHSV-tkgenetherapyonhepatictumorreferredas“bystandereffect”intherapeuticapproachhasnotbeenfoundinthisstudyandrequiredtobeexploredfurther.
