Analysis of key angiogenic factors to emphasize the impact of endostatin

分析关键血管生成因素以强调内皮抑素的影响

• 批准号: 17591481
• 负责人: YANO Motoki
• 金额: $ 2.24万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591481/
• 关键词: endostatin; antiangiogenesis; VEGF; VEGF受容体; インテグリン

We have established the endostatin transfection systems which showed the impact of antiangiogenesis and suppression of tumor growth. However the effect was not maintained for a long time. Finally the endostatin-tranfected animals died without tumor dormancy. There, also, have been no reports of effective clinical trials. We hypothesized the reasons he short effect of endostatin depended on up-regulation of some kinds of angiogenic factors. In the present study we have transfected mice lungs with endostatin gene and analyzed the VEGF gene expression. We used quantitative RT-PCR method to quantify the VEGF mRNA using GAPDH mRNA as an internal control. The both expression of Endostatin and VEGF mRNAs in the lung were apparent and the expression of VEGF mRNA in trasfection group (n=6) was higher than in cntol group (n=6) (p=0.0755 in Schffe's method in ANOVA, p=0.055 in Mann-Whitney U test). This mechanism was not unclear but the data was very important. This data may suggest that suppression of VEGF induced prolongation of effect of endostatin. Next we can try endostatin gene transfection with suppression of VEGF to prove the present data and achieve the tumor dormancy.

我们已经建立了内皮抑素转染系统，显示出抗血管生成和抑制肿瘤生长的影响。然而，这种效果并没有维持很长时间。最后，转染内皮抑素的动物无肿瘤休眠而死亡。也没有关于有效临床试验的报道。我们推测内皮抑素短效的原因与某些血管生成因子的上调有关。本研究用内皮抑素基因转染小鼠肺，分析VEGF基因的表达。我们采用定量RT-PCR方法，以GAPDH mRNA为内参，定量VEGF mRNA。内皮抑素和VEGF mRNA在肺组织中均有明显表达，转染组（n=6） VEGF mRNA表达高于对照组（n=6）（方差分析Schffe法p=0.0755， Mann-Whitney U检验p=0.055）。这一机制并不清楚，但数据非常重要。这一数据可能提示抑制VEGF可延长内皮抑素的作用。下一步，我们可以尝试转染内皮抑素基因，抑制VEGF，以证明目前的数据，实现肿瘤休眠。