摘要
AIM:Tumorangiogenesishasbeenshowntobepromotedbyvascularendothelialgrowthfactor(VEGF)viastimulatingendothelialcellproliferation,migration,andsurvival.BlockadeofVEGFsignalingbydifferentmeanshasbeendemonstratedtoresultinreducedtumorgrowthandsuppressionoftumorangiogenesisindistincttumorentities.Here,wetestedarecombinantadenovirus,AdsFIt1-3,thatencodesanantagonisticallyactingfragmentoftheVEGFreceptor1(Flt-1),forsystemicantitumoreffectsinpre-establishedsubcutaneousCRCtumorsinmice.METHODS:Murinecolorectalcarcinomacells(CT26)wereinoculatedsubcutaneouslyintoBalb/cmiceforinvivostudies.Tumorsizeandsurvivalweredetermined.293celllinewasusedforpropagationoftheadenoviralvectors.HumanlungcancerlineA549andhumanumbilicalveinendothelialcellsweretransfectedforinvitroexperiments.RESULTS:InfectionoftumorcellswithAdsFlt1-3resultedinproteinsecretionintocellsupernatant,demonstratingcorrectvectorfunction.Asexpected,thesecretedsFlt1-3proteinhadnodirecteffectonCT26tumorcellproliferationinvitro,butendothelialcellfunctionwasinhibitedbyabout46%ascomparedtotheAdLacZcontrolinatubeformationassay.WhenAdsFlt1-3(5×109PFU/animal)wasappliedtotumorbearingmice,wefoundatumorinhibitionby72%atd12aftertreatmentinitiation.Inspiteoftheseantitumoraleffects,thesurvivaltimewasnotimproved.AccordingtoreducedintratumoralmicrovesseldensityinAdsFIt1-3-treatedmice,theantitumormechanismcanbeattributedtoangiostaticvectoreffects.WedidnotdetectincreasedsystemicVEGFlevelsafterAdsFlt1-3treatmentandlivertoxicitywaslowasjudgedbyserumalanineaminotransferasedetermination.CONCLUSION:InthisstudyweconfirmedthevalueofasystemicadministrationofAdsFIt1-3toblockVEGFsignalingasantitumortherapyinanexperimentalmetastaticcolorectalcarcinomamodelinmice.
出版日期
2005年12月22日（中国期刊网平台首次上网日期，不代表论文的发表时间）
