溶血性链球菌制剂OK-432联合肿瘤冻融抗原诱导的树突状细胞瘤苗对小鼠前胃癌的抑瘤作用  

Inhibition of Implanted Mouse Forestomach Carcinoma by Dendritic-Cell-Based Vaccines Induced by OK-432 and Freeze-Thawed Tumor Cell Antigen

作　　者：倪秀雄[1] 曾真[1] 袁明洲[1] 张文豪[1] 刘丽燕[1] 

机构地区：[1]福建医科大学生理学与病理生理学系,福州350004

出　　处：《福建医科大学学报》2010年第6期412-416,共5页Journal of Fujian Medical University

基　　金：福建省自然科学基金(C0410020)

摘　　要：目的观察溶血性链球菌制剂(OK-432)联合肿瘤冻融抗原诱导的树突状细胞(DCs)瘤苗对小鼠前胃癌的体内抑瘤作用。方法分离小鼠骨髓单个核细胞(BMMCs),并在含10%胎牛血清、重组小鼠粒-巨噬细胞集落刺激因子(rmGM-CSF)、重组小鼠白细胞介素-4(rmIL-4)的培养体系中诱导培养,部分加入肿瘤冻融抗原和/或OK-432冲击,透射电镜下观察细胞形态,流式细胞仪检测细胞表面抗原CD83和CD86的表达情况。建立小鼠前胃癌移植瘤模型,随机分4组,分别从小鼠尾静脉注射磷酸盐缓冲液(PBS对照组)、未经肿瘤冻融抗原刺激的DCs(BM-DCs组)、经肿瘤冻融抗原刺激的DCs(TL-DCs组)和经OK-432联合肿瘤冻融抗原诱导的DCs(OK-DCs组),观察各组小鼠肿瘤体积及质量,并计算抑瘤率。结果于培养的第7天收集各组的DCs,OK-DCs呈典型成熟形态,其表面CD83和CD86的表达率高于BMMCs、BM-DCs、TL-DCs。体内实验显示,OK-DCs组移植瘤生长缓慢,瘤体积和质量均显著小于PBS对照组、BM-DCs组、TL-DCs组,体内抑瘤率为55.32%。结论 OK-432联合肿瘤冻融抗原诱导DCs成熟的方案制备的DCs瘤苗可明显抑制荷瘤小鼠前胃癌的生长。Objective To observe the in vivo inhibition of implanted mouse forestomach carcinoma（MFC） by dendritic-cell-based vaccines which were induced by penicillin-killed Streptococcus pyogenes（OK-432） and freeze-thawed tumor cell antigen,and to evaluate the application of these vaccines in specific immunotherapy for gastric carcinomas.Methods Mouse bone marrow mononuclear cells（BMMCs） were cultured in RPMI 1640 containing 10% FCS,rmGM-CSF and rmIL-4,pulsed with OK-432 and /or freeze-thawed tumor cell antigen.Morphological characters of DCs were observed under the optical microscope and the electron microscope;DCs surface molecules CD83 and CD86 were assayed by flow cytometry.MFC mouse models were established and were randomized into PBS control group,BM-DCs group（DCs induced from mouse bone marrow）,TL-DCs group（BM-DCs pulsed with freeze-thawed tumor cell antigen） and OK-DCs group（BM-DCs pulsed with freeze-thawed tumor cell antigen and OK-432）.The tumor volume,tumor weight and tumor inhibitotry rate were examined in different groups.Results DCs pulsed with OK-432 and freeze-thawed tumor cell antigen showed morphologically typical characters and expressed much more antigens CD83 and CD86 on the surface than BMMCs,BM-DCs and TL-DCs.The growth of implanted MFC tumors in OK-DCs group was greatly inhibited,and the tumor volume and weight were significantly lower than those in PBS,BM-DCs and TL-DCs group（P0.01）.The tumor inhibitotry rate in OK-DCs group was 55.32%.Conclusion OK-432 treatment combined with freeze-thawed tumor cell antigen pulsing is a simple and practicable way to induce maturation of DCs.The dendritic-cell-based vaccines which were induced by OK-432 and freeze-thawed tumor cell antigen can significantly inhibit the growth of implanted MFC tumors.

关 键 词：树突细胞 链球菌 血 毕西巴尼 抗原 肿瘤 癌症疫苗 胃肿瘤 疾病模型 动物 

分 类 号：R735.2[医药卫生—肿瘤]