关键词：神经胶质瘤反义治疗
神经胶质瘤为中枢神经系统常见肿瘤
一
目前认为肿瘤的发
反义基因治疗依据碱基互补原理
1.反义核糖核酸：反义RNA是将特异的反义基因连到特定的表达载体（质粒
2.核糖酶：Ribozyme是一类天然的
3.反义寡核苷酸：AONs及其衍
二
近年来，神经胶质瘤的反义治疗已取得许多可喜的成果。
Behl等在体外以AONs抑制恶性神经胶质瘤HTZ-146和HTZ-17两种细胞系的细胞增
将C6细胞向动物颅内接种后形成颅内肿瘤模型，然后立即行胰岛素样生长因子1（IGF-1）反义基因转染的C6细胞注射。4个
转化生长因子-β2（TGF-β2）由胶质瘤细胞自分泌产生，这种蛋白质为肿瘤免疫抑制因子，
反义核酸
AONs对细胞内蛋白也有影响。由于PDGF-B由C-sis原癌基因编码，故与C-sismRNA互补的AONs可抑制恶性胶质瘤A-172细胞系的细胞增生，AONs阻遏了A-172细胞内C-sis蛋白的再合成［13］。
在恶性胶质瘤细胞中，C-myb呈10倍扩增，而C-myb编码的蛋白又促使肿瘤细胞的增生，故与C-myb互补的AONs可用来抑制肿瘤细胞的增殖。将硫代磷酸AONs加至C-myb的5’帽启动区并培养48小时后发现，U87
蛋白激酶Cα（PKCα）介导许多生长因子
由于绝
尽管反义核酸治疗神经胶质瘤有广泛的开发前景，但真正用于临
1 MukhopadhyayT,RothJA.Antisenseregulationofoncogenesinhumancancer.CritRevOncog,1996,7:151-190.
2 DachsGU,DouphertyGJ,StratfordIJ,etal.Targetinggenetherapytocancer:areview.OncolRes,1997,9:313-325.
3 KawasakiH,MachidaM,KomatsuM,etal.Specificregulationofgeneexpressionbyantisensenucleicacids:asummaryofmethodologiesandassociatedproblems.ArtifOrgans.1996,20:836-848.
4 GibsonI.Antisenseapproachestothegenetherapyofcancer―‘Recnac’.CancerMetastasisRev.1996,15:287-299.
5 FlanaganWM,WagnerRW.Potentandselectivegeneinhibitionusingantisenseoligodeoxynucleotides.MolCellBiochem.1997,172:213-225.
6 AlamaA,BarbieriF,GagnoliM,etal.Antisenseoligonucleotidesastherapeuticagents.pharmacolRes,1997,36:171-178.
7 KashiharaN,MaeshimaY,MakinoH,Antisenseoligonucleotides.ExpNephrol.1998,6:84-88.
8 HallWA,FloresEP,LowWC.Antisenseoligonucleotidesforcentralnervoussystemtumors.Neurosurgery,1996,38:376-383.
9 BehlC,WinklerJ,BodahnU,etal.Autocrinegrowthregulationinneuroectodermaltumorsasdetectedwitholigodeoxynucleotidesantisensemolecules.Neurosurgery,1993,33:679-684.
10 TrojanJ,BlosseyBK,JohnsonTr,etal.Lossoftumorigenicityofratglioblastomadirectedbyepisome-basedantisensecDNAtranscriptionofinsulin-likegrowthfactor1.ProcNatlAcadSciUSA,1992,89:4874-4878.
11 JachimczakP,BogdahnU,SchneiderJ,etal.Theeffectoftransforminggrowthfactor-specificphosphorothioate-antisenseoligodeoxynucleotidesinreversingcellularimmunosuppressioninmalignantglioma.JNeurosurg,1993,78:944-951.
12 ResnicoffM,SellC.RubinM,etal.RatglioblastomacellsexpressinganantisenseRNAtotheinsulin-likegrowthfactor1（IGF-1）receptorarenontumorigenicandinduceregressionofwild-typetumors.CancerRes,1994,54:2218-2222.
13 NittaT,SatoK.Specificinhibitionofc-sisproteinsynthesisandcellproliferationwithantisenseoligodeoxynucleotidesinhumangliomacells.Neurosurgery,1994,34:309-315.
14 WelterC,HennW,TheisingerB,etal.Thecellularmyboncogeneisamplified,rearrangedandactivatedinhumanglioblastomacelllines,CancerLett,1990,52:57-62
15 AhmedS,MinetaT,MartuzaRL,etal.AntisenseexpressionofproteinkinaseCinhibitsthegrowththetumorigenicityofhumanglioblastomacells.Neurosurgery,1994,35:904-909.
16 LangfordLA,PiatyszekMA,XuR,etal.Telomeraseactivityinhumanbraintumors.Lancet,1995,346:1267-1268.
17 FengJ,FunkWD,WangSS,etal.Thecomponentofhumantelomerase.Science,1995,269:1236-1241.
18 NortonJC,PiatyszekMA,WrightWE,etal.Inhibitionofhumantelomeraseactivitybypeptidenucleicacidoligomers.NatureBiotech,1996,14:615-619.
19 KolbergR.Thebystandereffectingenetherapy:Great,buthowdoesitwork?JNIHRes,1994,6:62-64.
