抗肿瘤药物诱导肿瘤细胞凋亡机制的研究进展

31)2)(1),52059;2),252059).:pH.,,R730253167226634(2009)03200422060.1965LockshinWillianmsPCD(ProgrammedCellDeath,),.1972Kerr[1],(apoptosis),.,,,,.,.,,,[2].,.1992HickmanJA[3],,20.,7,160.,.1,.1.1DNA(G1)DNA(S)DNA(G2)(M).G1(G0),22320099()JournalofLiaochengUniversity(Nat.Sci.)Vol.22No.3Sep.20093:2008204226:(20773059;20543004);(J08LE02):,E2mail:[e-mail]..,.,,,[4].,,,[5].[6],G1S,G1,G1DNA,,,.Li[7]CyclinBmR2NA,CyclinB,CDC2,,G0.,.(NCTD),,.[8]NCTDK562,G2/M,M,,.,52(52FU)DNARNA,S,[9].,[10].Huwe[11]CDK(CDK/cyclin),G1G2/M.1.2,,.(cytosolicapartate-specificproteases,Caspases),.Caspase21,Caspases14,Caspasel14.Caspases,.Caspase28Caspase29Caspase233.Caspase28,[12].Caspase29,C,dATP1C,.Caspase23Caspase28Caspase29,.Caspase28Caspase29Caspase23,Caspase23(Caspases).ADP1Caspase23DNA[13].DNA,,.(TRAIL)UVAHaCaT,(PCF)UVAHaCaTTRAIL,UVACaspase28,TRAIL[14].[15]3,4-(MDMA)23(Caspase23).MDMA,Caspase23.1.3,,,,.,,.Bcl22P53C2myc.Bcl22/22,,DNA,,.Bcl22Bcl22BaxBcl2XBcl2wBakBadA1NR213Mcl21,BaxBakBcl2Xs,.Bcl22,,,343:DNA.BaxBcl22,Bax,Bcl22(Bcl22/Bcl22Bcl22/baxbax/bax),[16].[17]NCTDCaspaseBcl22,A3752s2,Caspase,Bcl22/BaxBcl2xl/Bax.,NCTDSASCa9222,.NCTDCa9222SAS,Bcl22Bcl2xl[18].[19]Bcl22(CHX)U251,Bcl22CHXU251,CHX.P53,.P53,P53,P53(wtP53)P53,,wtP53,P53[20].P53,P53DNA,P53,,.[21]P53,K562G0/G1,K562,P53.P16Rb,P16;P16DCDK4,CDK4,RB,G0G1,.RbRb.GFHepA,Rbp16,GFRbP16[22].C2myc,,,,.C2myc,C2myc,.C2mycDNA,,,.,C2myc,;,.[23]C2myc(ASODN)MKN245.C2mycMKN245C2myc.1.4,,.,,,().RNA,RNA.,,,;,,.,.,.,,.[24]hTERTTRAILSKOV3,RT2PCR.hTRETTRAIL,SKOV3,.44()22[25]RNA(hTRASODN)EC9706(AIF).hTRASODNEC9706,,AIF.hTRASODNEC9706,,,AIF.1.5(reactiveoxygenspecies,ROS),ROS,.ROS,.ROS,.ROSDNA.ROS,,.ROS,,,.ROS,,,,,.ROS,,.[26],L1210,DNA,;,(ROS);Bcl22/Bax,Caspase23Caspase29,Caspase28.L1210.[27],.CSmac(Diablo),.C,Bc122.(Bax)p53,.,,,.(PT),,PTCa2+(pH),,[28].,,,C.CApaf21Caspase29,(dATP),Caspase29,Caspase,[29].,NCTDMCF27,[30].[31],,Ca2+(PTP).K562,Caspase239C,K562[32].1.6pH,.,..,,DNA.[33]HelapH543:,Hela,pH7.116.51,,..,HelaHela.pH.2,,,..,,[34].,,,[35].,,,,,,.[1]KerrJFR,WyllieAH,CurrieAR.Apoptosis:abasicbiologicalphenomenonwithwiderangingimplicationsintissuekinetics[J].BrJCancer,1972,26:239245.[2]ItoM,MinamiyaY,KawaiH,etal.P2056Primarytumor2derivedTGF2B1inducesdendriticcellapoptosisinsentinellymphnodesofpatientswithnon2smallcelllungcancer[J].LungCancer,2005,49(2):129132.[3]HickmanJA.Apoptosisinducedbyanticancerdrugs[J].CancerMetastasisRev,1992,11(2):121139.[4]LiG,KimDH,KimTD,eta1.Protein2boundpolysaccharidefromPhellinuslinteusinducesG2/MphaserrestandapoptosisinSW480humancoloncancercells[J].CancerLett,2004,216(2):175181.[5],,,.[J].(),2001,14(4):8081.[6],.[J].,2005,6:6872.[7]LiXK,MotwaniM,TongW,eta1.Achineseherbalex.tract,inhibitscellgrowthbysuppressingtheexpressionofcyclineB1andin2hibitingCDC2kinaseactivityinhumancancercells[J].MolPharmacol,2000,58(6):12871292.[8],,,.[J].,2000,23:163164.[9],,.[J].,2006,19(6):697698.[10]WuX,OjimaI.Tumor2specificnoveltaxoid2monoclonalantibodyconjugates[J].CurrentMedChem,2004,11(4):429438.[11]HuweA,MazitschekR,GiannisA.Smallmoleculesasinhibitorsofcyclin-dependentkinases[J].AngewChemIntEd,2003,42(10):21002138.[12]TakimotoH,HasegawaM,YagiK,eta1.Proapoptoticeffectofadietarysupplement:watersolublechitosanactivatescaspase28andmodulatingdeathreceptorexpression[J].DrugMetabPhar2macokinet,2004,19(1):7682.[13]SongJaeJ,LeeYongJ..DifferentialcleavageofMst1bycaspase27/23isresponsibleforTRAIL2inducedactivationoftheMAPKsu2perfamily[J].CellularSignalling,2008,20(5):892906[14],,.UVAHaCaT[J].,2007,23(10):13751379.[15],,.MDMAcaspase23[J].,2007,(22)5:511513.[16]WeaverCyprianV,LiuShi2Ping.Differentiallyexpressedpro2andanti2apoptogenicgenesinresponsetobenzeneexposure:Immuno2histochemicallocalizationofp53,Bag,Bad,Bax,Bcl22,andBcl2winlungepithelia[J].ExperimentalandToxicologicPathology,2008,59(5):265272.[17],,,.A375S2[J].,2005,25(6):501503.[18]KokSH,ChengSJ,HongCY,eta1.Norcantharidininducedapoptosisinoralcancercellsisassociatedwithanincreaseofincreaseofproapoptotlctoantiapoptoticproteinratio[J].CancerLett,2005,217(1):4348.64()22[19],,,.Bcl-2U251[J].,2007,47(33):2426.[20]RobertaVitali,VincenzoCesi,BarbaraTanno,etal.Activationofp532dependentresponsesintumorcellstreatedwithaPARC2in2teractingpeptide[J].BiochemicalandBiophysicalResearchCommunications,2008,368(2):350356.[21],,,.P53K562[J].,2007,29(22):21602163.[22]IeeYH,ChengCM,ChangYF,eta1.ApoptinT1O8phosphorylationisnotrequiredforitstumorspe2cificnuclearlocalizationbutpartiallyaffectitsapoptoticactivity[J].BiochemBiophysResCommun,2007,354(2):391395.[23],,,.c2mycMKN245[J].,2007,14(24):18601863.[24],,,.TRAIL[J].,2007,23(12):11061109.[25],,,.hTR[J].:,2007,42(6):10411043.[26],,,.[J].,2007,42(12):12591265.[27],.[J].:,2005,32(3):176178.[28]OlavAGressner,BirgitLahme,AxelMGressner.Gc2globulin(vitaminDbindingprotein)issynthesizedandsecretedbyhepato2cytesandinternalizedbyhepaticstellatecellsthroughCa2+-dependentinteractionwiththemegalin/gp330receptor[J].ClinicaChimicaActa,2008,390(1):2837.[29],,,.[J].,2007,20(5):300302.[30]SangJL,LiZX,ZhangHJ.Apoptosisofbreastc