目的探讨蜂毒素对人肝癌细胞移植瘤在BALB/C裸鼠体内生长的影响。方法建立人肝癌BEL-7402细胞裸鼠皮下移植瘤模型,观察瘤内注射蜂毒素对肝癌细胞移植瘤在裸鼠体内生长的影响。应用HE染色观察肿瘤组织形态学变化,采用免疫组织化学法检测肝癌组织微血管密度(MVD),酶联免疫吸附法检测裸鼠血清白细胞介素-8(IL-8)的水平,Western blotting法检测裸鼠肝癌组织中血管内皮细胞生长因子(VEGF)的表达情况。结果荷瘤裸鼠瘤内注射蜂毒素剂量为40、60、80μg/kg时的抑瘤率分别为44.64%、62.86%、73.73%,药物处理组肿瘤体积明显小于模型组(P<0.01)。光镜下见蜂毒素各组肿瘤组织出现片状坏死,肿瘤间质内可见肿瘤血管,并有血管破坏现象。蜂毒素可明显降低裸鼠肝癌组织微血管密度,药物处理组IL-8和VEGF的表达显著低于模型组(P<0.01)。结论蜂毒素能够明显抑制人肝癌细胞裸鼠移植瘤的生长,其作用机制可能与下调IL-8和VEGF的表达,抑制肿瘤血管生成有关。

Objective To study the effect of melittin on the growth of human hepatoeellular carcinoma BEL一7402 cells xenograft in BALB／C nude mice and explore its possible mechanism of anti-tumor action invivo. Methods BEL一7402 Cells were subcutaneously transplanted into the right axial regions of nudemice.The xenograft tumor growth in mice was measured after introtumoral injection of melittin.Tumor tissue samples were taken and examined by light microscopy to assess the inhibitory effects of melittin.The microvessel density(MVD)was measured by SABC method of immunohistochemistry.The level ofinterlukin一8(IL一8)in serum of nude mice was detected by enzyme linked immunosorbent assay(ELISA)and the protein expression of vascular endothelial growth factor(VEGF)by Western blotting.ResultsWhen injected with 40,60,and 80弘g／kg of melittin,the inhibitory rates of tumor growth were 44.64％, 62.86％,and 73.73％,respectively.The tumor volume of xenograft in nude mice was significantlysmaller in melittin groups and Thlidomide(TLD)group than that in control group(P<0.01).Histopathological examination revealed the widespread necrosis with massive accumulation of infiltratinglymphocytes and plasmacytes in the tumors.The MVD,level of IL一8,and the expression of VEGF in the melittin groups were significantly lower than those in the control group(P<0.05 or P<0.01).Conclusion Melittin could inhibit the growth of tumor in vivo,which is probably related to inhibiting theangiogenesis in tumor by down-regulating the expression of IL一8 and VEGF.

国家自然科学基金资助项目(30472223)