人源性抗bFGF抗体抑制人黑色素瘤生长的作用研究  

The effect of human antibody against basic fibroblast growth factor on the growth of human melanoma

作　　者：杜超超[1] 亢中奎[1] 陈文慧[1] 潘磊[1] 宋其芳[1] 王宏[1] 黄建芳[1] 邓宁[1] 

机构地区：[1]暨南大学抗体工程研究中心广东省分子免疫与抗体工程重点实验室,广州510632

出　　处：《免疫学杂志》2013年第7期578-582,共5页Immunological Journal

基　　金：国家863项目(2009AA02Z112);中央高校基本科研业务费专项资金(21612112);国家自然科学基金青年基金项目(81202449);广东省科技计划项目(2012B010300016)

摘　　要：目的研究人源性抗bFGF抗体对人黑色素瘤A375细胞的体内外增殖抑制作用。方法体外培养人黑色素瘤A375细胞,CCK-8法检测人源性抗bFGF抗体对A375细胞增殖的影响;Western blot检测人源性抗bFGF抗体对bFGF下游信号通路中ERK1/2磷酸化的影响;建立裸鼠皮下移植瘤模型,通过记录各处理组裸鼠皮下移植瘤的体积、质量及裸鼠体质量变化,研究人源性抗bFGF抗体在体内对人黑色素瘤生长的抑制作用;免疫组化检测肿瘤组织内的微血管密度。结果 CCK-8实验结果表明人源性抗bFGF抗体能抑制A375细胞的生长,在800 ng/ml的质量浓度下,抑制率为24%;Western blot结果表明人源性抗bFGF抗体显著抑制FGFR下游信号通路中ERK1/2的磷酸化;裸鼠体内试验中,人源性抗体明显抑制了肿瘤的生长,抑制率为28.12%。免疫组化结果显示各组肿瘤组织中微血管密度均有下降。结论该株人源性抗体在体外可有效的抑制人黑色素瘤细胞的生长,并能在体内抑制肿瘤生长及血管新生。This study designed to investigate the inhibitory effects of human anti-bFGF antibody on human melanoma in vitro and in vivo. Firstly the proliferation inhibition of human melanoma cells by human anti-bFGF antibody was analyzed by CCK-8, and the phosphorylation level of ERK was detected by Western blot. Xenograft nude mouse model was established to study the inhibitory effects of human anti-bFGF antibody on melanoma in vivo; microvessel density （MVD） of the tumor tissue was analyzed by immunohistochemistry. The results of the proliferation inhibition showed that the proliferation of melanoma cells could be inhibited by human anti-bFGF antibody, and the inhibition rate was about 24% at the antibody concentration of 800 ng/ml; Western blotting results showed that ERK1/2 phosphorylation was inhibited by human anti-bFGF antibody, which demonstrated that human anti-bFGF antibody could inhibit the proliferation of tumor cells by inhibiting the ERK signal pathway. The tumor xenografts nude mice model showed that human anti-bFGF antibody could inhibit the tumor growth in vivo, and the inhibition rate was about 28.12%. Furthermore, the microvessle density of tumor tissue was decreased obviously. These results demonstrated that human anti-bFGF antibody could inhibit the proliferation of human melanoma cell in vitro and inhibit tumor growth and angiogenesis in vivo.

关 键 词：黑色素瘤 碱性成纤维细胞生长因子 人源性抗体 

分 类 号：R739.5[医药卫生—肿瘤]