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The effect of blockage of macrophage on tumor-suppresive activity of polyactin B

摘要撰写人 : TsingHua
浏览次数 : 20  词语: 300   出版日期: 九月 20, 1998
Theapplicationofbiologicalresponsemodifier(B RM)hasopenedanewwayfortreatingmanydiseases, especialymalignanttumorsinrecentyears.Great atentionhasbeenbroughttothetumorsuppresive efectsofsomeofBRM,modulationofpatient’simmu nologicalstatusandlessideefects,forexample ,SSM,OK432,andpolyactinA(PA),etc.1,2Polyact inB(PB),extractfromtheculturedβstreptococc ussupernatantmainlycomprisedofpolysacchari de,isanewkindofBRM.Ourpreviousexperimentsin vivoandinvitroshowedthatPBcouldstronglyinhi bitthegrowthofS180sarcomabyactivatingimmuno competentcels.3,4Inthepresentstudywefoundth atthehistopathologicalchangesofS180sarcoma withPBtreatmentwassimilartothoseinducedbyrT NF,andwiththeblockageofmacrophagesystembyTr ypanblue(TrB)thetumorsuppressiveefectofPB disappeared.METHODSAnimalsThirtytwoinbredB ALB/cmice,purchasedfromExperimentalAnimalC enter,theFourthMilitaryMedicalUniversity,w ereusedat8—12weeksofage(16—20g),theratiooff emaletomalebeing1∶1.FortyICRmice,purchased fromExperimentalAnimalCenter,Xi’anMedicalUn iversity,wereusedat8—12weeksofage(18—22g),t heratiooffemaletomalebeing1∶1.ExperimentsS1 80sarcoma(SC)growninKunmingmicewasremovedfo rthepreparationoftumorcelsuspensionandthetu morcelsuspensionwasadjustedto1×107cel/ml(th eviability>98%).Thetumorcels(1×106cel/mouse )wereinoculatedSCinthefrontrightbackoftheB ALB/cmice.Fivedayslater,whenthetumorcouldbe palpable,themicewererandomlydividedinto4gro ups:(1)controlgroup;(2)PBtreatedgroup;(3)Tr Btreatedgroup;(4)PB+TrBtreatedgroup,8micein eachgroup.Onday7aftertumorinoculation,tumo rssizewasmeasuredandcalculatedacordingtothe formula:V=ab22(V=thevolumeoftumor,a=thelong estdiameter,b=theshortestdiameter).ThenPBwa sinjectedatthedoseof100mg/kg·d1(ip)intothe miceingroups2and4,anddeionizedwaterwasinjec tedintothemiceingroup1.Twentyfourhoursand3 hoursbeforePBinjection,4mgand1mgTrB(ip)were injectedtothemiceingroups3and4.2Fivedaysaft erPBinjection,i.e.,onday12oftumorinoculatio n,thetumorsweremeasuredagain.Themiceweresac rificed,thetumorswereremovedandcutatthemaxi malsectionarea,andformalinfixedparafinemb eddedHEsectionswereprepared.Thetumortotala rea(TTA)andthetumornecroticarea(TNA)werees timatedwithpointcountingmethodusinganocula rgrid(1mm×1mm)undermicroscope.TheratioofTNA toTTAwascalculated.Similarly,ICRmicewereeve nlydividedinto4groups:(1)control;(2)PB;(3)T rB;(4)PB+TrB.S180sarcomacels(1×106/mouse)w ereinoculatedtoICRmice(ip).24hoursand3hours beforetumorinoculation,4mgand1mgTrB/percapi talwasinjected(ip)respectivelytothemiceingr oups3and4,then1mgTrBasmaintenancedoseevery5 days.Fromday1aftertumorinoculation,PBindose of100mg/kg·d1wasinjected(ip)tothemiceingro ups2and4,anddeionizedwatertothoseingroup1,u ntiltheICRtumorbearingmicedied.Thelifespa nandtheincreaserateoflifespan(ILS)werecalc ulated.4StatisticsStudentttestwasused.RESUL TSTheaveragesizeofS180sarcomaineachgroupond ay5ofPBadministrationislistedinTable1.Assho wninTable1,onday5afterPBtreatment,thesizeof tumorsdecreasedinturninPB+TrB,TrBandPBgroup s(Tumorsregresedcompletelyin3mice).Table1.T umorsizeofthemiceineachgrouponday5ofPBadmin istrationGroupNo.ofmiceTumorsize(x±s,mm3)tv aluePvalueControl81311.38±99.39PB5896.60±1 82.095.3721<0.001TrB81629.00±123.715.6617<0 .001PB+TrB81839.13±210.136.4217<0.01Thet umorin3of8miceregresedcompletely.Thus,5mice wereleft.PBgroupPB+TrBvsPB+TrBgroup,P<0.0 1(t=8.2506);TrBgroupvsPB+TrBgroup,P<0.05(t= 2.4374)ThecomparisonofTNA/TTAratioofeachgro upisshowninTable2.Table2.ComparisonofTNA/TT AratioofeachgroupGroupNo.ofmiceTNA/TTAratio (x±s)tvaluePvalueControl80.2622±0.0707PB50. 6428±0.21784.6380<0.001TrB80.2244±0.07021.0 739>0.05PB+TrB80.2594±0.08230.0729>0.05PB groupvsPB+TrBgroup,P<0.001(t=4.5496)Asshown inTable2,comparedwithothergroups,theratioof TNA/TTAinPBgroupismuchgreater.Theefectofmac rophagesystemblockageonthelifespanofS180sa rcomabearingmicetreatedwithPBisshowninTabl e3.Table3.ComparisonoflifespanandILSofmice ineachgroupGroupNo.ofmicelifespan(d)(x±s)Pvalue(tvalue)ILS(%)Control1018.0±3.71PB102.2±1.48<0.005(3.3249)23.33TrB1016.5±3.50>0.05(0.9292)-8.33PB+TrB1015.1±1.52<0.05(2.28

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