抗肿瘤药物的研究进展

()294JOURNALOFTHEGRADUATESVOL12942008SUNYAT2SENUNIVERSITY(NATURALSCIENCESMEDICINE)20083(,510080):,:,,,,:DNARNA,,,,,,3:2008-10-08:,,1982,,,2008,,ki2ki118576@sohu1com()41111DNA[1],DNADNA,Topo,Topo,Topo[2][3]2211C(PKC)PKCCa2+,(DAG),TPA(122O2tetradecanoylphorbol2132ac2etate)DAGPKC,PKCDAGTPA,PKC,,TPA,PKC,PKC,PKCPKC:PKCstauros2porine;PKCcalphostinC;PKCstaurosporinePKC,212(PTK)PTK,ATP,,,PTK,PTK[4]213A(PKA)PKA(cAMP),cAMPcAMP82PKA[5],ARNAcAMPcAMPA[6]8214-3/B/(PI3K2AKTmTOR)(mammaliantargetofRapamycin,mTOR),[1]PI3K/AKT2mTOR,,,mTOR,,PI3K2mTORmTOR(Rapamycin.Rap),,PI3K(Wortmannin,Wor)Wor;Rap,Rap,CCI.779RAD2001Rap,,,3,(TA),,,,,,,(VascularEndothelialGrowthFactor,VEGF)VEGFR,FDAAvastin,,angiostatinendostatin,[7][8]311Avastin(bevacizumab)AvastinGenentechVEGF[9],20042FDA,52Fu[10]AvastinVEGF,,FDA1,312,[11](MPI),.TIMP,(MMPs),MM:AE.941NCI,,9()4[12][13]P2MMP9MMP.12,,313angiostatinendostatin,,PEDF;[14];SchwannPEDF,[15]PEDF[16]PEDFPEDFp5317p1311[17],,PEDF4,,:,,,,,,,411TNFTNF,[18]TNF,,,,,412AAS2O3413(choleratoxin)(choleratoxin),PI3K/PKB,GSK23,CyclinD1(choleratoxin)PI3K/PKB,GSK23,CyclinD1,CyclinD1,-,CyclinD1,,[6]015,(CDKs)CDKs(Cyclins),CDKs,,CDK511Flavopiridol(NSC649890,L86-8275)Flavopiridol(NCI),cyclinD1cdkl24,G.s,AventisOneologyNCII[19]512UCN101[20]UCN-01NCI,T,G1G2UCN-01,Rb,UCN-01G1,CDK;UCN-01G2/M,CDK1CDK2,M,UCN-011(chk1),cdc25;DNA,[21][22];UCN-01E2F:[1]KehrerD,SoepenbergO,LoosWJ,etal.Modulationofeamptotheeinanalogsinthetreatmentofcancer:areview[J].AnticancerDrugs,2001,12(2):89-105.[2]GiovanellaBC,StehlinJS,HinzHR,eta1.Preclinicalevaluationoftheanticanceractivityandtoxicityof92nitro20(S)2camptothecin(Rubitecan)[J].JOneol,2002,20(1):81-88.[3].[M].:2,1991,1945-202.[4]DuffaudF,BlayJY.Gastrointestinalstromaltumorsandncatmcnl[J].Oncology,2003,65(3):187-197.[5]BradburyAW,CarterDC,MillerWR,etal.ProteinkinaseA(PK2A)regulatorysubunitexpres2sionincolorectalcancerandrelatedmucosa[J].BrJCancer,1994,69:738.[6]LiY,YinW,WangX,etal.CholeratoxininducesmalignantgliomacelldifferentiationviathePKA/CREBpathway[J].ProcNatlAcadSci,2007,104(33):13438-13443.[7]MatsumotoG,ShindoJ.Cancertherapybyenetherapywithangiostatin.DrugsToday(barc)[J],2001,37(12):815-821.[8]SledgeGWJ,MillerKD.Angiogenesisandantiangiogenictherapy[J].CurrProblCancer,2002,26(1):1-60.[9]GerberHP,Ferrara.Pharmacologyandpharmacodynamicsofbevacizumabasmonotherapyorincom211()4binationwithcytotoxictherapyinpreclinicalstudies[J].CancerRes,2005,65(3):671-680.[10]GingrasD,RenaudA,MousseauN,eta1.MatrixproteinaseinhibitionbyAE2941,amultifunc2tionalantiangiogeniccompound[J].AntiCancerRes,2001,21(1A):I45-J55.[11],.[J].,1998,18(8):368.[12]MoriK,KamiyamaY,KondohT,etal.PhaseIIstudyofcombinationofgemcitabineandcarbopla2tininadvancednon2smallcelllungcancer(aninterimreport)[J].GanToKagakuRyoho,2008,35(6):931-935.[13]TokuyamaJ,KubotaT,SaikawaYetal.TyrosinekinaseinhibitorSU6668inhibitsperitonealdis2seminationofgastriccancerviasuppressionoftumorangiogenesis[J].AnticancerRes,2005,25(1A):17-22.[14]EkET,DassCR,ChoongPF.PEDF:apotentialmoleculartherapeutictargetwithmultipleanti2canceractivities[J].TrendsMolMed,2006,12(10):497-502.[15]SeigelGM,Tombran2TinkJ,BecerraSP,etal.DifferentiationofY79retinoblastomacellswithpigmentepithelial2derivedfactorandinterphotoreceptormatrixwash:effectsontumorigenicity[J].GrowthFactors,1994,10(4):289-297.[16]FilleurS,VolzK,NeliusT,etal.Twofunctionalepitopesofpigmentepithelial2derivedfactorblockan2giogenesisandinducedifferentiationinprostatecancer[J].CancerRes,2005,65(12):5144-5152.[17]SasakiY,NaishiroY,OshimaY,etal.Identificationofpigmentepithelium2derivedfactorasadi2recttargetofthep53familymembergenes.Oncogene,2005,24(32):5131-5136.[18]AbeT,OhnoM,SatoT,etal.Differentiationinductioncultureofhumanleukemicmyeloidcellsstimulateshighproductionofmacrophagedifferentiationinducingfactor.Cytotechnology,1991,Suppl2:S75-S93.[19]LiY,TanakaK,LiX,etal.Cyclin2dependentkinaseinhibitor,flavopiridol,inducesapoptosisandinhibitstumorgrowthindrug2resistantosteosarcomaandEwing’sfamilytumorcells.IntJCancer,2007,121(6):1212-1218.[20]Senderow.Thecellcycleasatargetforcancertherapy:basicandclinicalfindingswiththesmallmoleculeinhibitorsflavopiridolandUCN-01[J].Oncologist,2002,7(Suppl3):S12-S9.[21]OwatT,Yoshinoh,Yoshimatsuk,etal.CellcycleregulationintheGIphase:apromisingtargetofthedevelopmentofnewchemoIherapeuticanticanceragents[J].CurrMedChem,2001,8(12):1487-1503.[22]WangS,WangZ,GrantS.Bryostatin1andUCN-01potentiate12beta2D2arabinofuranosyleytosine2inducedapoptosisinhumanmyeloidleukemiacellsthroughdisparatemechanisms[J].Pharmacol,2003,63(1):232-242.TheProgressofAnti2NeoplasticDrugsZhengXiaoke(ZhongshanSchoolofMedicine,SunYat2SenUniversity,Guangzhou510080)Abstract:Thereviewdisplaystherecentprogressofantineoplasticdrugs,includingcytotoxicones,onestarge2tingcellsignaltransduction,angiogenesisinhibitor,differentiationinducer,cellcycledependentproteinkinase(CDK)inhibitor,andsoon.Keywords:AntineoplasticDrugs21