bFGF单克隆抗体对卵巢癌移植瘤血管生成的抑制作用

目的:探讨碱性成纤维细胞生长因子(bFGF)在卵巢上皮性肿瘤中的表达强度与肿瘤血管生成之间的关系,及其单克隆抗体bFGFMAb对人卵巢癌移植瘤血管生成和肿瘤生长的影响。方法:(1)应用免疫组化法和图像分析系统研究bFGF在正常卵巢组织,良性、交界性和恶性卵巢上皮性肿瘤中的表达部位和强度;以及bFGF的表达强度与肿瘤新生血管的关系;(2)利用卵巢癌裸鼠皮下移植瘤模型,每周2次将不同浓度的bFGFMAb注射于瘤体周围,连续8周,每周测量肿瘤体积,绘制移植瘤生长曲线;对移植瘤组织行Ⅷ因子的免疫组化染色,测定肿瘤内微血管密度(MVD)。结果:(1)bFGF主要在卵巢上皮性肿瘤细胞浆内表达,在交界性和恶性肿瘤中,部分细胞同时存在核表达;bFGF在正常卵巢组织,良性、交界性和恶性卵巢上皮性肿瘤中的表达强度逐步增强,同时MVD逐步增高,二者呈正相关(P<0.001);(2)30、20、10μgbFGFMAb组移植瘤体积分别是对照组的31.34%、49.20%和71.25%,MVD分别是对照组的27.80%、52.37%和81.86%(P<0.05),其作用呈浓度依赖性。结论:bFGFMAb能明显抑制卵巢癌的血管生成和肿瘤生长,有望成为卵巢癌生物治疗的新方法。

The effect of bFGF monoclonal antibody on the growth and angiogenesis of ovarian cancer

Objective:To explore the expression of basic fibroblast growth factor (bFGF) in epithelial tumor tissues and the relationship between the expression of bFGF and intratumoral microvessel density (MVD),and to investigate whether the monoclonal antibody of bFGF (bFGF-MAb) could neutralize the effect of bFGF.Methods:(1)Immunohistochemistry and Mias-2000 picture analysis system were used to investigate expression of bFGF in 10 normal ovarian tissues,20 benign,20 borderline and 40 malignant epithelial tumor tissues,and MVD staining for factor VIII.(2)Forty BALB/c nude mice were implanted tumor tissues from established subcutaneous transplanted tumor model of human ovarian carcinoma.One week after implanted,1ml bFGF-MAb (30,20,10,0μg/ml)was injected subcutaneously twice a week.The volume of the tumors were measured weekly for 8 weeks,then the growth curves of transplanted tumors were draw.Eight weeks later MVD was measured.Results: (1)Expression of bFGF was mainly in cytoplasm,bFGF positive expression were found in cytoplasm and nucleus in several borderline and malignant tumor.The expression intensity of bFGF was significantly related to the degree of tumor malignance,and also significantly related to MVD (P<0.001).(2)The average volume of tumors in 30,20 and 10μg/ml bFGF-MAb group was 31.34%,49.20% and 71.25% of the control group respectively;MVD was 27.80%,52.30% and 81.86% of the control group respectively.The effect of bFGF-MAb on tumor growth and angiogenesis was concentration dependent.Conclusion: bFGF-MAb can inhibit the proliferation,invasion and angiogenesis of ovarian cancer markedly.It can be used potentially in the biological treatment of ovarian cancer.