FGFR1嵌合蛋白疫苗抗小鼠纤维肉瘤血管生成的实验研究.doc

文档介绍：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
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作者:郭峻莉,郑少江,郑少萍,罗志飞
【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(Western 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、 ± 、 ± 、 ± ± ();与对照组相比,Ag43/FGFR1组肿瘤体积明显变小(),存活时间明显延长(),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﹤)。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。
【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
[ABSTRACT] Objective: To explore the antitumor effect of immunotherapy with a binant Ag43/FGFR1 chimeric protein ine in a mouse Meth A a 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/FGFR1immunized group than in Ag43immunized group、FGFR1immunized group and NS group ( ± versus ± versus ± and ± , P﹤). The tumor volume was significantly smaller in Ag43/FGFR1immunized group than in the control groups (P﹤), and the survival time was significantly longer in Ag43/FGFR1
immunized group than in the control groups (P﹤). 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﹤). Conclusion: These results demonstrated that the Ag43/FGFR1 protein ine could induce the production of antitumor autoimmunity, which further