中效原理在体外抗癌药物定量分析中的应用

:2003208208;:2003211217:1.400010;2.1,2,1ApplicationofMedian2effectPrincipleinGuantitativeAnalysisofAntitumorAgentsinVitroCHENShu1,TANGWei2xue2,LOUShi2feng11.DepartmentofHematology,TheSecondHospitalofChongqingUniversityofMedicalSciences,Chongqing400010,China;2.DepartmentofPathophysiology,ChongqingUniversityofMedicalSciencesAbstract:ObjectiveSynergisticandantagonisticeffectofcombinedantitumoragentswereanalyzedquantita2tivelywithmedian2effectprincipleinvitro.MethodsThemedian2effectprincipleandMTTmethodwereusedinHL260.ResultsVincristineandcytarabinumcytotoxicactivityoftheindividualandcombineddrugsenhancedasdrugconcentrationincreased.Thesequenceofadministrationdidnotinfluencethecytotoxicactiv2ityofthecombinedantitumordrugs.Theratioofdrugconcentrationwasafactortoinfluencethekillingef2fect.Theinteractionoftheagentswassynergisticatlowerconcentration,andantagonisticathigherconcen2tration.ConclusionThecombineddrugsinteraction(CI1)wassynergisticatlowerconcentrationandan2tagonisticathigherconcentration.Theratioofdrugconcentrationisasignificantfactorthatcaninfluencethekillingeffect.Keywords:HL260;Median2effectprinciple;Cytorabinum;Vincristine;Combinationindex(CI):MTT,(,)HL260,,,,,,:HL260;;;;:R733.7;R730.53:A:100028578(2004)05202702030,,,,,[1],(Chou2Talalay)[225](HL260),11.1(HL260)10%()RPMI1640(GIBCO)(0.1%),37,5%CO21.2(cytorabinum,Ara2c)(),1.430mmol/L0.715mmol/L0.357mmol/L0.178mmol/L0.089mmol/L(Vincristine,VCR)(),4.85010-3mmol/L2.42010-3mmol/L1.21210-3mmol/L0.60010-3mmol/L0.30010-3mmol/L1.3MTT[6]1.3.1HL2605104/ml,200l,960722004315(8),(8)(3)1.3.296,20l;11,20l(1,10l),37,5%CO23,1.3.3Ara2c24hVCR,VCR24hAra2c,37,5%CO23,1.3.4Ara2cVCR1/10(1.21210-3mmol/L),VCRAra2c1/10(0.357mmol/L),37,5%CO23,3,1.4(Bio2RadE2500)A570nm(fa)=1-ODODfa/fu=(DDm)mlg(fa/fu)=mlgD-mlgDma=-mlgDmb=mx=lgDy=lg(fa/fu)y=bx+afa,fu=1-faD,mDm,0.5,Dm(lgDm=-a/m),D=Dm(fa/fu)1/m,CI=D1Dx1+D2Dx2+D1D2Dx1Dx2,D1D2x,Dx1Dx2x=0,=1CI1,CI=1,CI122.1,1m,Dmr,2CI,31(fa),(CI)1(mmol/L)(fa)(n=9)Ara2cVCRAra2c+VCR(1.430)0.888(4.85010-3)0.898(1.435)0.872(0.715)0.818(2.42010-3)0.800(0.717)0.854(0.357)0.787(1.21210-3)0.697(0.358)0.809(0.178)0.635(0.60010-3)0.611(0.179)0.757(0.089)0.448(0.30010-3)0.427(0.090)0.6152mDmr(m)(Dm)mmol/L(r)Ara2c0.79596.08010-30.982VCR0.7410.38810-30.995Ara2c+VCR0.50925.42010-330.9693Ara2c25.33610-3mmol/L,VCR0.08410-3mmol/L3(fa)(CI)(fa)0.950.900.800.750.700.600.500.400.300.200.10(CI)3.332.071.220.980.870.680.480.390.270.190.111Ara2cVCR2.2,453,,DNADNA,,S,G1/SS/G2[7],M,17220043154(n=9)Ara2c+VCR(mmol/L)Ara2c24hVCR24h1.4350.8720.0370.7410.1190.8710.0430.7170.8540.0280.7270.0920.8230.0440.3580.8090.0380.7170.0860.7990.0970.1790.7570.0220.7020.0540.7320.0360.0900.6150.0370.5910.0490.6060.083t,P0.05,,,,,M,[7]HL260,,,HL260,,2Ara2cDm5(mmol/L)(n=9)Ara2cVCRVCR/Ara2cfaCIVCRAra2cVCR/Ara2cfaCI1.4301.21210-3140.8701.194.85010-30.357140.8663.770.7151.21210-3120.8501.232.42010-30.357120.8342.100.3571.21210-3110.8071.461.21210-30.357110.8001.410.1781.21210-311/20.7611.490.60010-30.35711/20.7770.880.0891.21210-311/40.6391.640.30010-30.35711/40.6230.4596.08010-3mmol/L,25.33610-3mmol/L,3.792;VCRDm0.38810-3mmol/L,0.08410-3mmol/L,3.619,,,,,HL260,Ara2cVCR,,5Ara2cVCR1/10(1.21210-3mmol/L);VCR0.60010-3mmol/LAra2c1/10(0.357mmol/L)(Ara2cVCR11/2,11/4),VCR0.60010-3mmol/LAra2c1/10(Ara2cVCR11,12,14),,(31),fa0.8(),CI1,;fa0.75()CI1,,,,,,:[1],.[M].:,1999.54271.[2]ChouTC,TalalayP.Quantitativeanalysisofdose-effectsrela2tionships:thecombinedeffectofmultipledrugsonenzymein2hibitors[J].AdvEnzymeRegul,1984,22:27255.[3]TingChaoChou,RobertJM,YouZhiTong,etal.ComputerigedquantitationofsynergismandantagonismofTaxol,Topotecan,andCisplatinagainsthumanteratocarcinomacellgrowth:aratio2nalapproachtoclinicalprotocoldesign[J].JournaloftheNationalcancerInstitute,1994,86(20):151721524.[4]ScottHK,DavidP,ChristopherAB,etal.CytotoxiceffectsofTopotecan.Combinedwithvariousanticanceragentsinhumancancercelllines[J].JournaloftheNationalCancerInstitute,1996,88(11):7342741.[5]HayleyMM,PatrickGJ.SynergisticInteractionbetweenpacli2taxeland82Chloro2adenosine3,52Monophosphateinhumano2rarianCarcinomaCellLines[J].ClinCancerRes,1999,5(1):2152220.[6],,.MTT[J].,1992,17(2):1032108.[7],,.[M].:,2000.39267.[:]2722004315