中文摘要：

目的：探讨蜂毒素抗裸鼠骨肉瘤的作用及对肿瘤血管生成拟态的影响。方法：体外建立matrigel胶三维培养系统，观察蜂毒素对骨肉瘤UMR-106细胞血管生成拟态（vasculogenic mimicry，VM）形成的影响；建立裸鼠骨肉瘤胫骨移植瘤模型，分为0．9％氯化钠溶液组、蜂毒素组（320ug／kg）、顺铂组（2n,g／kg），瘤内注射给药10d，观察小鼠的肿瘤抑制率和瘤体质量抑制率；用CD34与PAS双重染色观察骨肉瘤VM密度；免疫组织化学法和Western印迹法检测肿瘤组织中缺氧诱导因子1α（hypoxia inducible factor-1α，HIF—1α）、基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）蛋白的表达。结果：蜂毒素在体外可以破坏骨肉瘤细胞的血管状结构；体内对骨肉瘤的瘤体质量抑制率为38．92％，体积抑制率为43．04％。蜂毒素组VM密度、HIF-1α、MMP-2蛋白的表达水平均明显低于0．9％氯化钠溶液组（P〈0．01）。结论：蜂毒素能明显抑制UMR-106骨肉瘤裸鼠移植瘤的生长，其机制可能与下调HIF-1α、MMP-2蛋白的表达、抑制骨肉瘤VM有关。

英文摘要：

Objective： To investigate the antitumor effects of melittin on UMR-106 cells with osteosarcoma xenografis in nude mice and its action on vasculogenic mimicry （VM） in vitro and in vivo. Methods： A three-dimensional cell culture system was formed on matrigel coats in vitro. Inhibitory action of melittin on the VM of UMR-106 cells was observed in vitro. Osteosarcoma was orthotopically transplanted in nude mice. The mice were randomly divided into three groups： normal saline （NS）-treated group, melittin group （ 320 ug/kg） and DDP-treated group（2 mg/kg）. The drug was administered intratumorally for 10 d. The tumor volume and weight inhibition ratio were calculated,respectively. The VM density in tumor tissues was detected by CD34 and PAS double staining in vivo. The expressions of hypoxia-inducible factor-1 α（ HIF-1 α） and matrix metalloproteinase-2 （MMP-2） proteins were determined by immnnohistochemical staining and Western blot. Results：Melittin broke down the mesh and round architectonic of VM in osteosarcoma in vitro. The tumor weight inhibition ratio was 38.92% and the volume inhibition ratio was 43.04%. The VM density and the expressions of HIF-1α and MMP-2 proteins were decreased in the melittin group than that in the NS-treated group （P 〈 0.01 ）. Conclusion： Melittin markedly inhibites the growth of osteosarcoma UMR-106 xenografts in nude mice. The mechanism may be due to down-regulation of HIF-1α and MMP-2 expression and the inhibition of VM.