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

血管抑制素基因治疗鳞状细胞癌体内研究

• 批准号: 11672023
• 负责人: MATSUMOTO Goichi
• 金额: $ 2.5万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672023/
• 关键词: angiostatin; gene therapy; squamous cell carcinoma; 血管新生; (1)アンジオスタチン; (2)扁平上皮癌; (3)VEGF; (4)VEGFR-2; (5)血管新生

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.

肿瘤生长是一个依赖血管生成的过程，以抑制血管生成为目标的治疗策略在理论上是有吸引力的。血管抑素在体外能有效抑制血管内皮细胞的增殖，在体内能抑制肿瘤的生长。我们现在发现，通过将编码小鼠血管抑素的基因转移到小鼠鳞状细胞癌NRS-1和SCC-VII细胞中，肿瘤血管生成的平衡发生了变化，从而抑制了体内的肿瘤生长。血管抑素对肿瘤的抑制伴随着肿瘤血管的显著减少和肿瘤细胞的大量凋亡。而血管抑素基因的表达不影响血管内皮细胞中血管内皮生长因子及其受体的表达。其抑制新生血管的机制可能不依赖于血管内皮生长因子：血管内皮生长因子-R2复合体。我们的数据可能为血管抑素基因治疗口腔癌提供了一种有用的方法。

项目成果

Matsumoto G.,Ohmi Y.,and Shindo J.: "Angiostatin gene therapy inhibits the growth of murine squamouse cell carcinoma In vivo."Oral Oncology. (in press).

Matsumoto G.、Ohmi Y. 和 Shindo J.：“血管抑制素基因疗法在体内抑制小鼠鳞状细胞癌的生长。”口腔肿瘤学。

Matsumoto Goichi, Ohmi Yasushi, and Shindo Junichi.: "Angiostatin gene therapy inhibits the growth of murine squamouse cell carcinoma in vivo"Oral Oncology. (in press).

Matsumoto Goichi、Ohmi Yasushi 和 Shindo Junichi.：“血管抑制素基因疗法抑制体内小鼠鳞状细胞癌的生长”口腔肿瘤学。