NO在抗肿瘤治疗中的作用

NO在抗肿瘤治疗中的作用(中国医学科学院基础医学研究所、中国协和医科大学基础医学院药理室,北京　100005)1996-12-31:,33,,;,60,,R979.1;R730.5,NO,,1,(M)NO,NO,,NO,DNA2NO,NO,,,,,,,,,,NONO,1NO1.1NO,NO,NO;(IFN-)TNFIL-1IL-2(nitricoxidesynthase,NOS)NO(guanylatecyclase,GC),GC,cGMP,,3NO,4,M51.2NOMHibbs(1987)M,NOM,NO,NOFe-S,-,,DNA,DNANO,6,BeckmanNO(O2)(ONOO-),ONOO-(OH)NO-27OH,,DNARNA,NOMIFN-TNF-IL-1IL-2MNOS;,IFN-(EGF)(TGF-)(PDGF)NOS8M,,NOS(iNOS),NO;NOTNFIL-291.3,,NOS10,iNOS,L-(L-arginine,L-Arg)NG--L-(NG-monomethyl-L-arginine,L-NMMA)N--L-(N-nitro-L-argininemethylester,L-NAME)NO,11NO492中国药理学通报　ChinesePharmacologicalBulletin　1997Dec;13(6):492～6,,,NOSN--L-(N-nitro-L-arginine,L-NNA),32P-,/;,NO(NOdonors,NO-d)(Sydnonimines),1214C-L-Arg14C-L-Western,1314NOS,NOS,,13Rubens(1994)NOS,NOSNO14JenkinsMiNOScDNApBAN2,DLD-1,NO,,iNOS,,NO,,15,NO1.4NOCO,NADPHP450,-2COCONO,cGMP,,3NO,GCFe2+,NOS,2%,,,NOS,NO16,NOO2ONOO-,OH,,2NO2.1(reactiveoxygenspecies,ROS),OHROS,/,,OH,,NOHoward-Flanders(1957),NONO,Liebmann(1994)/NO(ethylamine/NO,DEA/NO)NO-d,NO,,DEA/NONO,OH,XOH:O2OH;(O3);O2NOONOO-,OHSODO2,NO,ONOO-OHOHDNAO2,NO,NO,,,OH,,NO13,14NO,OH,NOO2,NONOS,,NOS2.217TNFM,NOS,,NO,9IL-2NOMNO2-,NO5-FU493中国药理学通报　ChinesePharmacologicalBulletin　1997Dec;13(6),,5-FUNO,2.3Browman(1993),,,Bjermer(1990),,,Higman(1993),NO,,NO,NONOCO,,,NO,,NOS-(S-nitarosothiol),NO-dNO2.4,,,,EGF,,ROS,NOROSNOONOO-OH,ROS,OHTNFMiNOS,NO18,Captopril,Amiforstine,,,,19,NOTNF,,,NMDACa2+,Ca2+,NOSNO,15NOONOO-,NOO2NOTNF-,iNOSNOOH,NOS(cNOS),iNOS,NO20,NO,,,NOS3NONO,OH,NO,NONO,,NO3.1NONO-dNO,5:Molsidomine,NO,;:,,,21;Sydnonimines,SIN-1,,22SydnoniminesNO,,S-,NO;:NO,DEA/NO/NO(Spermine/NO,SPER/NO),,NO,5494中国药理学通报　ChinesePharmacologicalBulletin　1997Dec;13(6)NONOSNO()()DNA()NO()()DNANONO,Captopril,NO23captoprilamiforstinetem-polROS,NOO2,ONOO-,NO,ROStempol,SOD,,243.2NOL-ArgNOS,NOSL-NMMAIL-2TNFtirapazamineNOS,,25NOC,NOS4,NOROS,NONO,,,NO,,,cNOSiNOSNO,,,NO,,NO,参考文献1SrivatanakulP,OhshimaH,KhlatMetal.OpisthorchisviverriniinfestationandendogenousnitrosaminesasriskfactorsforcholangiocarcinomainThailand.IntJCancer,1991;48:82152NguyenTD,BrunsonCL,CrespiBWetal.DNAdamageandmutationinhumancellsexposedtonitricoxideinvitro.ProcNatlAcadSciUSA,1992;89:303043,.NO-cGMP.基础医学与临床,1996;16:408194RadomskiMW,VallanceP,WhitleyGetal.Plateletadhe-siontohumanvascularendotheliumismodulatedbyconsti-tutiveandcytokineinducednitricoxide.CardiovascRes,1993;27:13825MaragosCM,WangJM,HrabieJAetal.Nitricoxide/nu-cleophilecomplexesinhibittheinvitroproliferationofA375melanomacellsvianitricoxiderelease.CancerRes,1993;53:56486MoncadaS,PalmerRMJ,HiggsEAetal.Nitricoxide:Physiology,pathophysiology,andpharmacology.Pharma-colRev,1991;43:109427BechmanJS.Thedouble-edgedroleofnitricoxideinbrainfunctionandsuperoxidemediatedinjury.JDevPhysiol,1991;15:5398NakayamaI,KawaharaY,TsudaTetal.Angiotensininhibitscytokine-stimulatedinduciblenitricoxidesynthaseexpressioninvascularsmoothmusclecells.JBiolChem,1994;269:1628339BaudryN,VicautE.Roleofnitricoxideineffectsoftumor495中国药理学通报　ChinesePharmacologicalBulletin　1997Dec;13(6)necrosisfactor-alphaonmicrocirculationinrat.JApplPhysiol,1993;75:2392910ButteryLDK,SpringallDR,AndradeSPetal.Inductionofnitricoxidesynthaseintheneovasculatureofexperimentaltumourinmice.JPathol,1993;171:311911AndradeSP,HartIR,PiperPJ.Inhibitorsofnitricoxidesynthaseselectivelyreduceflowintumour-associatedneo-vasculature.BrJPharmacol,1992;107:1092512WoodPJ,StratfordIJ,AdamsGEetal.Modificationofen-ergymetabolismandradiationresponseofamurinetumourbychangesinnitricoxideavailability.BiochemBiphysResCommun,1993;192:5051013ThomsenLL,IawtonFG,KnowlesRGetal.Nitricoxidesynthaseactivityinhumangynecologicalcancer.CancerRes,1994;54:1352414Arias-DiazJ,VaraE,Torres-MeleroJetal.Nitrite/nitrateandcytokinelevelsinbronchoalveolarlavagefluidoflungcancerpatients.Cancer,1994;74:15465115JenkinsDC,CharlesGI,ThomsenLLetal.Rolesofnitricoxideintumorgrowth.ProcNatlAcadSciUSA,1995;92:4392616SnyderSH.Janusfaceofnitricoxide.Nature,1993;364:57717HillSA,LonerganSJ,DenekampJetal.Vincaalkaloids:anti-vasculareffectsinamurinetumoursystems.BrJCan-cer,1993;29:1320418PendinoKJ,LaskinJD,ShulerRLetal.Enhancedproduc-tionofnitricoxidebyratalveolarmacrophagesafterinhala-tionofapulmonaryirritantisassociatedwithincreasedex-pressionofnitricoxidesynthase.JImmunol,1993;151:719620519RubinP,GashDM,HansenJTetal.Disruptionoftheblood-brainbarrierastheprimaryeffectofCNSirradiation.RadiotherOncol,1994;31:516020DeBelderAJ,RadomskiMW,WhyHJFetal.Nitricoxidesynthaseactivitiesinhumanmyocardium.Lancet,1993;341:84521RadomskiMW,ReesDD,DutraAetal.S-nitrosoglu-tathioneinhibitsplateletactivationinvitroandinvivo.BrJPharmacol,1992;107:745922BohnH,SchonafingerK.OxygenandOxidationpromotethereleaseofnitricoxidefromsydnonimines.JCardiovascPharmacol,1989;14:S61223KalayciogluM,BukowskiR.Clinicalstatusofthenewcy-toprotectiveagent,amifostine.Oncology,1994;8:152324HahnSM,TochnerZ,KrishnaCMetal.Tempol,astablefreeradicalisanovelmurineradiationprotector.CancerRes,1992;52:1750325BrownJM.SR4233(Tirapazamine):anewanticancerdrugexploitinghypoxiainsolidtumours.BrJCancer,1993;67:116370-4c