抗VEGF抗体对骨肉瘤OS-732细胞血管生成及其肿瘤细胞增殖、凋亡的影响

目的：探讨阻断血管内皮生长因子（Vascular endothelial growth factor,VEGF)的血管生成作用对骨肉瘤OS-732细胞及血管内皮细胞增殖、凋亡的影响。方法：应用鸡胚绒毛尿囊膜（CAM）模型，通过解剖显微镜血管计数，光镜HE染色，原位末端标记及PC-NA免疫组化检测观察VEGF抗体对骨肉瘤血管生成及肿瘤增殖，凋亡状态的影响。结果：VEGF抗体组肿瘤区血管数目及瘤细胞数显著低于PBS对照组，肿瘤细胞凋亡指数显著高于PBS对照组，增殖指数两组差异不明显，同时VEGF抗体组凋亡的微血管内皮细胞增多，增殖期微血管内皮细胞少见。结论：VEGF抗体能显著抑制骨肉瘤OS-732血管生成，抑制内皮细胞增殖，促进内皮细胞凋亡，可能是VEGF抗体发挥抗血管生成作用的途径之一，并可能通过抑制血管形成而促进肿瘤细胞凋亡，最终达到抑制瘤细胞生长的作用。

Effects of anti-VEGF antibody on angiogenesis and proliferation and apoptosis of human osteosarcoma cell line OS-732

Objective To investigate the effects of anti-VEGF antibody on angiogenesis and on the proliferation and apoptosis of the osteosarcoma OS-732 cells and the vascular endothelial cells. Methods The effects of polyclonal antibody against VEGF on OS-732 induced angiogenesis were observed by a stero-microscope and light microscope in a tumor model of the chick embryo chorioallantoic membrane (CAM). Furtheremore, the proliferation and apoptosis of tumor cells and vascular endothelial cells were examined by TdT-mediated dUTP nick and labelling (TUNEL) and immunohistochemical staining by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). Results The number of both the newly formed vessels in the tumor and the tumor population were significantly decreased in the anti-VEGF antibody group as compared with that of the PBS control group. The apoptotic index for tumor cell was higher in the anti-VEGF antibody treated group than that in the negative control group, but the proliferation index was not significantly different between them. At the same time, increased apoptotic cells and decreased proliferation in vascular endothelial cells were also noted. Conclusion VEGF antibody can inhibit the neovascularization of OS-732, probabaly by the mechanism of inhibi- ting the proliferation and promoting the apoptosis of vascular endothelial cells, further, might be contributive to the apoptosis of tumor cells and result in suppression of tumor growth.