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1、血管内皮生长因子反义寡核昔酸联合低分子11!月干素治疗小鼠膀胱癌作者：范海涛，王秀岩，柴红梅，刘禄成【摘要】目的探讨血管内皮生长因子(VEGF)反义寡核昔酸和低分子肝素法安明单用或联合对小鼠膀胱癌、转移的抑制作用。方法制备小鼠膀胱癌模型40只，随机分为对照组、VEGF反义寡核昔酸(ASODN)组、VEGF错义寡核苜酸(MS0DN组)、低分子肝素(LMWH组)及联合治疗组，每组8只，分别给予生理盐水、VEGFASODN、VEGFMSODN、法安明及VEGFASODN+法安明皮下注射，隔日1次，共15次。检测皮下移植瘤变化和盆腔淋巴结转移率；应用免
2、疫组织化学的方法检测肿瘤组织微血管密度(MVD)；应用Western印迹的方法检查肿瘤组织VEGF蛋白表达。结果MSODN、ASODN、LMWH和联合治疗组的抑瘤率分别为2.1%、33.6%、20.1%和45.3%；盆腔淋巴结转移率分别为62.5%、25%、25%和12.5%；Western印迹法检测显示，对照组和MSODN组表达较高水平的VEGF；ASODN组和联合治疗组MVD分别为(11.34±3.03)和(10.01±1.25),与对照组(21.23±4.01)和MSODN组(18.21±3.36)相比,差异有统计学意义(P<0.0
3、1)；LMWH组MVD为(13.04±6.53),较对照组和MSODN组降低，差异有统计学意义(P<O.05)。结论VEGFASODN和法安明具有下调VEGF表达，抗血管生成作用；两者联合应用有协同抗肿瘤作用。【关键词】膀胱癌；血管内皮生长因子；低分子量肝素Abstract:Object!veToinvestigatetheinhibitoryeffectofvascularendothelialgrowthfactor(VEGF)antisensedigonucleotidesor/anddalteparinsodium(fragmin
4、)ontumorgrowthandmetastasisofmicebladdercancer.MethodsFortymicewithbladdercancerwererandomizedlydividedintofivegroups:controlgroup,VEGFantisenseoligonucleotides(ASODN)group,VEGFmismatchsenseoligonucleotides(MSODN)group,1owmolecularweightheparin(LMWH)group,andcombinedgroup.So
5、diumchloride,VEGFASODN,VEGFMSODN,fragmin,andVEGFASODNplusfragminweregivenrespectively(onceeverytwodays,15timesaltogether).Thevolumeandweightofsubcutaneoustumorsweremeasured,andtherateofpelviclymphonodemetastasisweredetectedbyHEstaining.Themicrovesseldensity(MVD)intumormasswa
6、smeasuredbyinimunohistochemistrystaining.VEGFproteinlevelintumortissuewasdetectedbyWesternblotassay.ResultsAftertreatment,thetumorgrowthinhibitoryrateswere2.1%,33.6%,20.I%and45.3%,andtherateofpe1viclymphonodemetastasiswere62.5%,25%,25%andl2.5%inMSODN,ASODN,LMWH,andthecombine
7、dgroup,respectively.WesternBlotindicatedthattherewashighlevelVEGFinMSONDandControlgroup.MVDofMSODN,ASODN,LMWH,thecombinedgroupandControlgroupwas(18.21±3.36),(11.34±3.03),(13.04±6.53),(10.01±1.25)and(21.23±4.01).Differencewassignificant.ConclusionVEGFASODNandfragminmaydownreg
8、ulateVEGFgeneexpressionandinhibitangiogenesis.Combineduseoffragmincanenhanc
