蜂毒素对人肝癌裸鼠移植瘤的抗血管生成作用

目的探讨蜂毒素对人肝癌裸鼠移植瘤生长的影响及其抗血管生成作用。方法建立人肝癌裸鼠皮下移植瘤模型,观察蜂毒素对肿瘤生长的影响。采用免疫组织化学法,检测肿瘤组织微血管密度（microvessel density,MVD）及碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF）、缺氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）和核转录因子κB（nuclear factorκB,NF-κB）的水平。结果蜂毒素低、中、高剂量组相对肿瘤增殖率分别为48.78%、38.33%和33.82%。与生理盐水组比较,蜂毒素处理组肿瘤体积明显缩小（P〈0.01）。免疫组化结果显示,蜂毒素可降低肿瘤组织MVD,且蜂毒素处理组bFGF、HIF-1α和NF-κB蛋白水平明显低于生理盐水组（P〈0.01）。结论蜂毒素可抑制裸鼠皮下移植瘤的生长,其作用机制可能是降低NF-κB活性,抑制HIF-1α转录,进而下调bFGF表达,最终阻碍肝癌血管生成。

Effects of Melittin on Angiogenesis of Human Hepatocellular Carcinoma BEL-7402 Cell Xenografts in Nude Mice

Objective To study the effects of Melittin on the growth and angiogenesis of human hepatocellular carcinoma BEL-7402 cells xenograft in BALB/C nude mice.Methods The xenografts derived from BEL-7402 cells were established in BALB/C nude mice.The xenograft tumor growth in mice was measured after introtumoral injection of Melittin.SABC method of immunohistochemistry was used to measure microvessel density(MVD) and the expression of basic fibroblast growth factor(bFGF),Hypoxia inducible factor-1α(HIF-1α) and nuclear factor κB(NF-κB).Results When injected introtumorally with 40、60 and 80 μg/kg of Melittin,the relative tumor proliferation rate were 48.78%、38.33% and 33.82% respectively.The tumor volume of xenograft of nude mice was significantly smaller in Melittin groups than in normal saline(NS) control group(P<0.01).MVD of Melittin-treated groups was significantly lower than that of NS control group(P<0.01).Immunohistochemical technique showed the expression of bFGF,HIF-1α and NF-κB of Melittin-treated groups was down-regulated significantly as compared with NS control group(P<0.01).Conclusion Melittin could inhibit the growth of human hepatocellular carcinoma BEL-7402 cell xenografts in Nude Mice.The inhibition of angiogenesis by the down-regulation of b-FGF,HIF-1α and NF-κB expression might play a key role in the anti-neoplastic effect of Melittin.