Ag43/FGFR-1嵌合蛋白疫苗抗小鼠纤维肉瘤血管生成的实验研究  

Study on the anti-angiogenesis mechanism induced by a Ag43/FGFR1protein vaccine in a mouse Meth A fibrosarcoma model

作　　者：郭峻莉[1,2] 郑少江[1] 郑少萍[1] 罗志飞[1] 

机构地区：[1]海南医学院病理学教研室肿瘤研究所,海南海口571101 [2]华中科技大学同济医学院病理学系,湖北武汉430030

出　　处：《海南医学院学报》2009年第5期403-406,共4页Journal of Hainan Medical University

基　　金：国家自然科学基金资助项目(30660055);海南省自然科学基金资助项目(30864);海南省卫生厅指导性项目(琼卫2006-28)

摘　　要：目的:利用Antigen43(Ag43)/成纤维细胞生长因子Ⅰ型受体(FGFR-1)重组嵌合蛋白作为疫苗,了解其是否具有抑制小鼠肿瘤生长的作用,并初步探讨其作用机理。方法:40只BALB/c雌性小鼠接种Meth A细胞后第7天,随机分为Ag43/FGFR-1蛋白免疫组(AF组)、Ag43蛋白免疫组(Ag43组)、FGFR-1蛋白免疫组(FGFR-1组)和生理盐水对照组(NS组)4组,每组10只,观察免疫治疗后的荷瘤小鼠肿瘤体积和生存曲线,分别用免疫组织化学方法检测肿瘤组织微血管密度(MVD),免疫印迹(W est-ern blot)方法检测抗自身FGFR-1的抗体,酶联免疫斑点试验(ELISPOT)检测分泌抗自身FGFR-1抗体的B淋巴细胞的数量。结果:Ag43/FGFR-1组与FGFR-1蛋白、Ag43蛋白、生理盐水对照组肿瘤组织MVD计数分别为11.9±2.3、59.6±3.8、60.6±1.2和61.9±3.4(P<0.01);与对照组相比,Ag43/FGFR-1组肿瘤体积明显变小(P<0.01),存活时间明显延长(P<0.01),血清中发现含有抗自身FGFR-1的抗体且发现小鼠脾脏中分泌抗自身FGFR-1抗体的B淋巴细胞数目明显增多(P(0.01)。结论:Ag43/FGFR-1蛋白质疫苗能够诱导荷瘤鼠产生特异性免疫反应,从而抑制肿瘤血管生成和肿瘤的生长。Objective： To explore the anti-tumor effect of immunotherapy with a recombinant Ag43/FG- FR-1 chimeric protein vaccine in a mouse Meth A fibrosarcoma model. Tumor volume and survival rate of the mice were observed in 3-day intervals. Methods： Microvessel density （MVD） was detected by immunohistochemistry. Autoantibodies against self-FGFR-1 were detected by Western blot. The anti-FGFR-1 antibody-producing B cells （APBCs） were detected by enzyme-linked immunospot （ELISPOT） assay. Results： MVD was significantly lower in Ag43/FGFRl-immunized group than in Ag43-immunized group,FGFR1-immunized group and NS group （11.9 ± 2.3 versus 59.6 ± 3.8 versus 60.6± 1.2 and 61.9 ± 3.4, P 〈 0.01 ）. The tumor volume was significantly smaller in Ag43/FGFR-1-immunized group than in the control groups （P 〈 0.01 ） , and the survival time was significantly longer in Ag43/FGFR-1-immunized group than in the control groups （P 〈 0.01 ）. Antibodies against self-FGFR-1 were identified in Ag43/FGFR-1-immunized group. Compared with the three control groups, the numbers of APBCs in Ag43/FGFR-1-immunized group were significantly increased（P 〈 0.01 ）. Conclusion： These results demonstrated that the Ag43/FGFR-1 protein vaccine could induce the production of antitumor autoimmunity, which further inhibit angiogenesis and growth of solid tumor.

关 键 词：成纤维细胞生长因子I型受体 Ag43基因 蛋白质疫苗 肿瘤血管生成 

分 类 号：R393.11[医药卫生—基础医学] R730.26