摘要
目的研究血管内皮生长因子(VEGF)表达与骨肉瘤血管生成和预后的关系,以及VEGF抗体抑制骨肉瘤细胞OS-732诱导血管生成的作用和可能机制,为以VEGF为靶点治疗骨肉瘤提供实验依据。方法应用免疫组化和形态计量方法,检测80例骨肉瘤VEGF表达、肿瘤微血管密度(MVD),以及OS-732血管生成相关因子的表达。进一步应用鸡胚绒毛尿囊膜(CAM)模型观察VEGF抗体对OS-732诱导血管生成及肿瘤细胞生长的抑制作用。结果(1)骨肉瘤VEGF表达与肿瘤微血管密度(MVD)及预后密切相关。(2)OS-732表达VEGF和bFGF,而且VEGF表达强度明显高于bFGF,OS-732具有很强的诱导血管生成能力。(3)VEGF抗体干预实验结果显示VEGF抗体组肿瘤区血管密度明显低于PBS对照组,细胞凋亡指数显著高于PBS对照组,而增殖指数两组差异无统计学意义。同时,VEGF抗体组凋亡的微血管内皮细胞增多,增殖期内皮细胞少见。结论VEGF是骨肉瘤重要的血管生成因子,其表达可能是评估骨肉瘤预后的一项有价值的指标。VEGF抗体能够抑制内皮细胞增殖,促进内皮细胞凋亡,显著抑制骨肉瘤OS-732血管形成,并可能通过抑制血管形成而促进肿瘤细胞凋亡,达到抑制瘤细胞生长的作用。该结果提示VEGF可以作为骨肉瘤抗血管生成治疗的潜在靶分子。
Objective To investigate the expression of vascular endothelial growth factor （VEGF） and its relationship with prognosis in huamn osteosarcomas and the effect and probable mechanism of inhibition of angiogenesis by VEGF antibody,and to furtherly provide an experimental evidence for the application of VEGF as a molecular target in antiangiogenic therapy of osteosarcoma. Methods The expression of VEGF and intratumoral microvascular density （MVD） in 80 osteosarcomas and osteosarcoma cell OS-732 was detected by immunohistochemical staining. The effect of a polyclonal antibody against VEGF on angiogenesis and tumor growth was investigated with a tumor model of the chick embryo chorioallantoic membrane （CAM）. Results （1）The expression of VEGF was significantly associated with microvascular density and prognosis in osteosarcoma. （2）The positive expressions of VEGF and bFGF were detected in OS-732, moreover the VEGF expression was much higher than the bFGF expression. OS-732 was strongly angiogenitic in the CAM model. （3）VEGF antibody administration in tumor-bearing chick embryo resulted in growth arrest of xenografts and a marked reduction in the new capillaries which converged upon the tumor. The tumor cell apoptotic index was higher in the anti-VEGF antibody treated group than the negative control group, but the proliferation index was not significant difference between them. At the same time, increased apoptosis and decreased proliferation in endothelial cell （EC） were also observed. Conclusion These findings support the hypothesis that VEGF is an important angiogenitic factor in osteosarcoma, may be a useful prognostic indicator of osteosarcomas. VEGF antibody is able to inhibit the angiogenesis induced by OS-732 obviously, probably by the mechanism of inhibition of endothelial proliferation and promotion of their apoptosis. The results indicate that VEGF may be a potential targeted molecular in the anti-angiogenesis therapy of osteosarcoma.
出处
《重庆医学》
CAS
CSCD
2006年第15期1369-1372,共4页
Chongqing medicine
基金
国家自然科学基金资助(NO30340044
NO30472004)
第三军医大学校科研基金资助(NOXG200357)
关键词
骨肉瘤
血管生成
血管内皮生长因子
osteosarcoma
angiogenesis
vascular endothelial growth factor
