树突细胞联合_榄香烯对小鼠胰腺癌治疗的实验研究

_榄香烯对小鼠胰腺癌治疗的实验研究

树突细胞联合β2榄香烯对小鼠胰腺癌治疗的

实验研究

殷朔　谭广　罗海峰　程雷　王忠裕

大连医科大学附属一院普外科,　　[摘要]　背景与目的:树突细胞(Dendriticcells,DC)胞,DCDC的MHC2I分子提呈并诱导的特异性CTL免疫反应抗癌作用显著。DCβ2榄香烯对小鼠胰腺癌治疗作用。方法并鉴定,负载肿瘤抗原后制备成疫苗。分别观察DC诱导的CTL和β。体内观察DC疫苗联合β2榄香烯对小鼠胰腺癌的抑制作用。结果:

α可使成熟的树突状细胞比例增DC,利用TNF2

加,MHC2Ⅱ、CD86等表面分子的表达较单纯DC组显著增强。负载凋亡抗原后DC诱导的特异性CTL体外

β2对胰腺癌细胞有显著杀伤作用,效靶比30∶1时,诱导的CTL对胰腺癌细胞抑制率达93%。榄香烯对癌细胞增殖

抑制明显,DC疫苗与β2榄香烯联合治疗可明显抑制荷瘤小鼠肿瘤的生长,使其生存期延长,联合治疗组生存期为49.4天,与单纯β2榄香烯组(24.8天)、DC疫苗(38.5天)、DC组(20.7天)及对照组(17.5天)相比有显著差异(P<0.05)。结论:经凋亡肿瘤细胞致敏的DC回输荷瘤小鼠可激发宿主针对特异肿瘤的Th1及CTL免疫应答,以DC介导的免疫反应联合中药的治疗方法可成为抗肿瘤的崭新且有效手段。

β2[关键词]　树突状细胞;　榄香烯;　胰腺癌;　免疫治疗;　小鼠

中图分类号:R73236　　文献标识码:A　　文章编号:100723639(2007)0120050204

Treatmentofmurinepancreaticcarcinomabydendriticcellvaccinescombinedwithβ2elemene　

YINShuo,TANGuang,LUOHai2feng,CHENGLei,WANGZhong2yu(DepartmentofGeneralSurgery,TheFirstAffiliatedHospital,DalianMedicalUniversity,DalianLiaoning116011,China)

Correspondenceto:TANGuang　E2mail:tanguang009@sina.com[Abstract]Backgroundandpurpose:Dendriticcells(BM2DCs)haverecentlybeenfoundtobethemostpowerful

andspecifictumorantigenpresentingcells.DCvaccineisoneofthetreatmentoptionsthatisbeingdeeplyinvestigatedandmighthavepotentialforclinicalapplication.SpecificCTLimmuneresponsestoapoptoticantigenoftumorcell,whichisin2ducedandpresentedbyDCwithMHC2Imolecule,showstrongeranti2tumoreffect.Thepurposeofthisstudyistoexplorethetreatmentofβ2elemenecombinedwithimmuneresponsesinducedbybonemarrow2deriveddendriticcellsafteracquiringapoptoticantigenforpancreaticcarcinoma.Methods:TheC57BL/6murineDCswerepulsedwithapoptotictumorcellanti2gen.TheimmunotherapeuticeffectsinducedbyDCvaccinescombinedwithβ2elemeneonmurinepancreaticcarcinomawereassessed.CTLimmuneresponseandproliferatinginhibitionwereassessedinvitro;survivalperiodandtumorregres2sionwereobservedinvivo.Results:AntigenpresentingmatureDCswithhighlyexpressedsurfacemoleculesMHC2II、CD83、

αCD86wereinducedbyTNF2.CTLresponseinducedbyDCafteracquiringapoptoticantigenshowstrongcytotoxicactivityagainstpancreaticcancercells.Proliferationinhibitionrateisabout93%wheneffect/targetratiois30∶1,β2elemenecould

efficientlyinhibittheproliferationofcancercellsinvitro.Thetumorsizeregressedmarkedlyandthesurvivalperiodwas

β2elemenegroup,comparedtotheotherfourgroupsmarkedlyprolongedformicetreatedbyDCvaccinescombinedwith

(P<0.05).Conclusions:CTLandTh1immuneresponsestimulatedbyDCvaccinespulsedwithapoptoticantigenhaveverystrongcytolyticactivityagainstpancreaticcancercells.Thedentriccellvaccinescombinedwithelemenemaybeoneofthenewmethodsthatmayhaveaneffectiveimmuneandchemotherapeuticfunctionagainsttumorcellsimplantedinmice.

β2elemene;　pancreaticcarcinoma;　immunetreatment;　mice[Keywords]　dendriticcell;　

　　美国30年来胰腺癌的发病率已达10/10万人,

基金项目:辽宁省科技厅自然基金资助项目(No.20042138)。通讯作者:谭广　E2mail:tanguang009@sina.com

其病死率居恶性肿瘤的第4位,在我国近年来胰腺癌的发病率也在不断地上升,上海市区1999年已增

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至10.1/10万人。胰腺癌临床治疗效果不满意。

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