肿瘤多药耐药性与中药逆转研究

,(,100700)[],,,[];;;;[]R730.53[]A[]1672-1977(2003)03-0221-05StudyontumorcellsmultidrugresistanceanditsreversionbyChineseherbsCHENXin-Yi,LIUJiang-Tao(DepartmentofOncologyandHematology,DongzhimenHospital,BeijingUniversityofTraditionalChineseMedicine,Beijing100700,China)[ABSTRACT]Multidrugresistance(MDR)isanimportantbiologicalbehavioroftumorcellsinchemotherapy.Anditisalsooneofthemajorcausesofclinicalchemotherapyfailure.Accordingtotheliteratureathomeandabroad,andcombiningwiththeresultsofanthorsinvestigations,thispapermainlydiscussesthemechanismoftumorcellsMDRanditsreversionbyChi-neseherbs.[KEYWORDS]neoplasms;multidrugresistance;drugs,Chineseherbal;reversiontherapy;review[JChinIntegrMed,2003,1(3):221-225](multidrugresistance,MDR),,,MDR11.11.1.1PJuliano1976P(permeabilityglycoprotein,Pgp)Pgp,,,Pgp,ATPATP,ATP,,Pgpmdr(mdr1mdr2),mdr1,Pgp,,mdr1,mRNA,Pgpmdr1mRNAPgp,,,[1,2]1.1.2Cole[3],PgpMDR,(multidrugresistance-associatedprotein,MRP)MRPMRP,MRP[4],MDR[5]Brock[6]H69/VP16,MRPPgpVersantvoort[7]MRP-S-(GST)1.1.3(lungresistance-associatedprotein,LRP)Scheper[8]PgpSW-1573MDRSW-1573/2R120,LRP1.21.2.1CC(phosphokinaseC,PKC)Ca2+,MDR,PgpPKC1222003913JChinIntegrMed,Sep2003,Vol.1,No.3[](2000002611)[](1954-),,.E-mail:[e-mail],PKCmdr1,PKCmdr1PgpMDR1.2.2DNADNA(DNAtopoisomerase,Topo),,DNA,DNA[9]Topo,,Topo,,DNATopo[10]1.2.3(glutathione,GSH)-S-(glutathione-S-transferase,GST)GSH,GST,GSH,,(TS)(ALDH)(MPO)(DHFR)1.31.3.1,,,,1.3.2,NF-Bbcl-2bcl-XerbB2/neup53c-fosc-fun,22.12.1.1(tetrandrine,TTD)(dauricine,DRC)(daurisoline,DRS)TTD,[11],10-6mol/LTTD(daunorubicin,DNR)(vincristine,VCR),[12],10-6mol/LTTDK562/AO2DNR,K562/S[13],10mol/LTTD(MCF-7/Adr)(adriamycin,ADR),100,VCRBEC-7402,13TTD,[14]K562/SADRK562/AO2,TTDDNR[15]TTDMCF-7/AdrMCF-7,KBKBV200,1mol/LTTDMCF-7/AdrADR,IC50MCF-7,KB,[16],TTDADR,G2M,HL60,TTDADRDRCTTD[17]DRC2.5mol/L5.0mol/L10.0mol/LVCRBEL-74023.05.49.7,MCF-7/Adr,Pgp5mol/LDRC(veropamil,VRP)3.610.0mol/LDRCKBV200VCRVCRBEL-7402DRSADRPgpMCF-7/Adr,PgpDRSPgpKBV200VCRBEL-7402,DRSVRPDRSVRPPgp,MDR,[18]Ys-96,,MDRMCF-7/AdrKBV200IC50Ys-96(bisbenzylisoquinoline,BBI)BBIMDR,Shiraishi[19](cepha-2222003913JChinIntegrMed,Sep2003,Vol.1,No.3ranthine,CPR)KBMDRVCRDNRD,ADR,CPR,MDRCPRPgp,Akiyama[20]CPRPgpChen[21],BBI,P388/R-84,ADRPgp[3H]azidopinePgp,BBI,2.1.2(tetramethylpyrazine,TMP),[22],TMPK562K562/AdrDNA,100mg/L9.9%TMPK562/AdrADR,K562DNA,TMP[23],TMPADRADR,EAC/Adr,0.25mg/LADRIC5052.16%TMPADREAC/AdrGST,EACGST[24],TMPADREAC/Adr,TMPADREAC/Adr,TMPEAC/Adr[25],100mg/LTMP3.2mg/LA(chondroitinsulfateA,CsA)(HT)HL60/HTIC50[26],TMPMDRHL60/VCRTMPVCR,DNR[27],TMPMKN45,24.4%28.5%,,TMPBBI,Pgp,Pgp,,,PKC,mdr1mRNATMPBBIVRP,2.1.3,[28],MDR,,,ADR,ADRMDR,K562/AO2HL-60/ADR5.75.6DNR,[29]2.1.4,[30],(teapolyphe-nols,TP)SW1116/ADRVRP,TPADRDNRVCR,TPADRADRTPVRP,,TP,[31],TP2.1.5,,[32][33]K562ADRK562/Adr,Bcl-2Pgp,,,DNR,Bcl-2Pgp,2.22.2.1R1[34],MTTR1()ADRMCF-7/Adr,ADR,MCF-7,MCF-7,MCF-7/AdrADR,R1ADR,PgpMoAbC219,MCF-7/Adr100%,R1,PgpWesternblot,R1MCF-7/Adrmdr1mRNA,190R1mdr1mRNA[35]3222003913JChinIntegrMed,Sep2003,Vol.1,No.3,R12.2.2R3[36]R3,MDR,130R3MCF-7/AdrADR720,VRPR3Rho-123,Pgp,,MDR,VRPMDR,,,,;,;,GSTPgp;,,,,MDR[]1ChevillardS,PouillartP,BeldjordC,etal.Sequentialassessmentofmultidrugresistancephenotypeandmeas-urementofS-phasefractionaspredictivemarkersofbreastcancerresponsetoneoadjuvantchemotherapy[J].Cancer,1996,77(2):292-300.2DeckerDA,MorrisLW,LevineAJ,etal.Immunohisto-chemicalanalysisofP-glycoproteinexpressioninbreastcancer:clinicalcorrelations[J].AnnClinLabSci,1995,25(1):52-59.3ColeSP,BhardwajG,GerlachJH,etal.Overexpres-sionofatransportergeneinamultidrug-resistanthu-manlungcancercellline[J].Science,1992,258(5088):1650-1654.4VersantvoortCH,WithoffS,BroxtermanHJ,etal.Resistance-associatedfactorsinhumansmall-celllung-carcinomaGLC4sub-lineswithincreasingadriamycinresistance[J].IntJCancer,1995,61(3):375-380.5ZamanGJ,FlensMJ,VanleusdenMR,etal.Thehumanmultidrugresistance-associatedproteinMRPisaplasmamembranedrug-effluxpump[J].ProcNatlAcadSci,1994,91(19):8822-8826.6BrockI,HipfnerDR,NielsenBS,etal.Sequentialcoex-pressionofthemultidrugresistancegenesMRPandmdr1andtheirproductsinVP-16(etoposide)-selectedH69smallcelllungcancercells[J].CancerRes,1995,55(3):459-462.7VersantvoortCH,BroxtermanHJ,BagrijT,etal.Regulationbyglutathioneofdrugtransportinmulti-drug-resistanthumanlungtumourcelllinesoverex-pressingmultidrugresistance-associatedprotein[J].BrJCancer,1995,72(1):89-89.8ScheperRJ,BroxtermanHJ,SchefferGL,etal.Overex-pressionofaM(r)110,000vesicularproteininnon-P-glycoprotein-mediatedmultidrugresistance[J].CancerRes,1993,53(7):1475-1479.9WithoffS,JongDeS,VriesDeEG,etal.HumanDNAto-poisomerase:biochemistryandroleinchemotherapyre-sistance[J].AnticancerRes,1996,16(4A):1867-1880.10VassetzkyYS,AlghisiGC,GasserSM.DNAtopoi-somerasemutationsandresistancetoanti-tumordrugs[J].Bioessays,1995,17(9):767-774.11,,,.[J].,1994,15(5):256-257.12,,.[J].,1995,15(3):543-546.13,.[J].,1995,40(20):1901-1904.14,.[J].,1995,16(5):235-237.15,,,.[J].,1996,21(6):369-371.16,,.HL60[J].,1996,17(2):179-181.17,.[J].,1996,15(6):410-414.18