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1、XX大學(xué)畢業(yè)論文胸昔激酶系統(tǒng)血管靶向抗肝癌效應(yīng)的機(jī)制姓名:2014年6月25日作者:李寶金,張超,周玉梅,郝穎,劉曉平,區(qū)慶嘉【關(guān)鍵詞】肝腫瘤;KDR啟動(dòng)子;基因治療;重組腺病毒;胸昔激酶系統(tǒng);HepG2細(xì)胞;裸鼠,Balb/c[Abstract]AIM:ToexplorethetherapeuticefficacyandmechanismofHSVtkfortargetingangiogenesisagainsthepatocellularcarcinoma.METHODS:ByusingpAdeasysystem,recombi
2、nantadenoviruscontainingkinasedomainreceptor(KDR)orcytomegalovirus(CMV)promotercontrolledHSVtkgene(AdKDRtkandAdCMVtk)wasconstructed.TheviruswasusedtoinfectKDRexpressedhumanumbilicalvenousendothelialcells(HUVEC)andKDRunexpressedHepG2.Followingadministrationofganciclovir
3、(GCV),thesurvivalrateofgenetransfectedHUVECandHepG2wasevaluatedbyusingMTTmethod.Hepatocarcinomasweretransplantedin32Balb/cmicewithHepG2cells,whichweresubsequentlydividedinto4groups:GCVgroup(1),Adgroup(II),AdCMVtkgroup(III)andAdKDRtkgroup(IV).Thenselectiveadministration
4、ofrecombinantadenovirusorAdintratumorallywasperformedinallrats.GCVwasgivenatadoseof100mg/(kgd)ipinthefollowingdaysandfor10d.Microvesseldensity(MVD)oftumorinallthetreatedanimalswascheckedwiththeimmunohistochemicalmethodsandtumorburdenwasassessed10dbeforeandafterthelastG
5、CVadministration.RESULTS:ThepAdeasysystemproducedahightiteroftherecombinantadenovirus[(1x1013)pfu/L]?Whenthemultiplicityofinfection(MOI)was100,withincreasingGCVconcentrationfrom0upto50mg/L,thesurvivalrateofAdKDRtktransfectedHUVECandHepG2decreasedfrom(90.7±4.5)%and(91.8
6、±4.3)%to(2&9±5.7)%and(75.4±2.9)%,respectively(P0.01),whilethesurvivalrateofAdCMVtktransfectedHUVECandHepG2declinedfrom100%to(17.6±2.5)%and(23.2±5.7)%,respectively(P0.05).ComparedwithgroupI.therewasadecreaseoftumorweightby(14.7±3.2)%ingroupIIIand(23.6±5.6)%ingroupIV,res
7、pectively;andtherewasadistinctdifferencebetweengroupIIIandIV(P0.05).ThemedianMVDwas37.4±8.6,30.6±7?8,27?6±7?1,10?7±4.1(microvessels/mm2)ingroupI,II,IIIandIV,respectively;andthereweresignificentdifferencesbetweengroupIIIandII(P0.05),IVandII(P0.01),IVandIII(P0.01).CONCLU
8、SION:KDRpromoterHSVtkgenemayeffectuallyrestrainthegrowthoftumorviatargetingangiogenesisofhepatocellularcarcinomawitht