A study of angiostatin gene therapy for squamous cell carcinoma in vivo

肿瘤生长是一个血管生成依赖性过程，旨在抑制血管生成的治疗策略在理论上具有吸引力。血管抑素已被证明在体外有效地抑制内皮细胞增殖和在体内抑制肿瘤生长。我们现在表明，转移到小鼠鳞状细胞癌NRS-1和SCC-VII细胞的编码小鼠血管生成抑制素的cDNA的基因转移在肿瘤血管生成的平衡抑制肿瘤生长在体内。血管抑制素转染的肿瘤的抑制伴随着血管分布的显著减少和许多凋亡肿瘤细胞的存在。然而，转染的血管抑素cDNA不影响血管内皮中VEGF和VEGF-R2的表达。抑制新生血管形成的机制可能不依赖于VEGF：VEGF-R2复合物。我们的研究结果为血管抑素基因治疗口腔癌提供了一种有效的方法。

Tumor growth is an angiogenesis dependent process and therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive. Angiostatin has been shown to potently inhibit endothelial proliferation in vitro and tumor growth in vivo. We now show that a shift in the balance of tumor angiogenesis by gene transfer of a cDNA coding for mouse angiostatin into mouse squamous cell carcinoma NRS-1 and SCC-VII cells supresses tumor growth in vivo. The inhibition of an angiostatin transfected tumor was accompained by a marked reduction in vascularity and the presence of many apoptotic tumor cells. However, transfected-angiostatin cDNA does not affect the expression of the VEGF and VEGF-R2 in the vascular endothelium. The inhibition mechanisms of neovascularization may be mediated independent of VEGF : VEGF-R2 complex. Our data may provide a useful approach for human oral cancer therapy by gene therapy with angiostatin.