Effects of antisense vascular endothelial growth factor complementary DNA on the growth of human glioma cells.

反义血管内皮生长因子互补DNA对人胶质瘤细胞生长的影响。

• 批准号: 07671538
• 负责人: SUGIYAMA Satoru
• 金额: $ 1.47万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671538/
• 关键词: Tumor angiogenesis; VEGF; antisence; gliomas; ヒトglioma; 血管内皮細胞増殖因子; 脳腫瘍; アンチセンスオリゴ; 遺伝子治療

Tumor angiogenesis is controlled by vascular endothelial growth factor, platelet-derived growth facter, and fibroblast growth factor. These growth factors involve a combination of events including the production of inhibitors, and angiogenic factors that have a chemotactic and mitogenic effect on endothelial cells.Vascular endothelial growth factor (VEGF) is a heparin-binding growth factor that promotes angiogenesis in solid tumor, including brain tumors such as glioblastoma.As an approach to the development for gene therapy of brain tumors, we have examined antisense VEGF gene expression in a variety of human glioma cells, and interrupted the VEGF/VEGF reseptor paracrine pathway.T98G,U138MG,U87MG,PNET cells were transfected with EBV expression vector pCEP4 bearing an antisense VEGF cDNA.The stable transfectant cell and control cell clones were analyzed for growth in monolayr. The stable transfectant cells appeared phenotypically indistinguishable from normal cells and control cells. However, the growth rates of the stable transfectant cells differed markedly from the control cells.Here, we show that antisence VEGF can be successfully used to control tumor growth and may provide the antiangiogenic gene therapy.

肿瘤血管生成受血管内皮生长因子、血小板衍生生长因子和成纤维细胞生长因子的调控。血管内皮生长因子（Vascular endothelial growth factor，VEGF）是一种肝素结合的生长因子，在实体瘤（包括胶质母细胞瘤等脑肿瘤）中具有促进血管生成的作用。我们已经检测了反义VEGF基因在多种人脑胶质瘤细胞中的表达，并阻断了VEGF/VEGF受体旁分泌途径。T98 G，U138 MG，U87 MG，用携带反义VEGF cDNA的EBV表达载体pCEP 4转染PNET细胞，分析稳定转染细胞和对照细胞克隆的生长情况。单层稳定的转染细胞表现为与正常细胞和对照细胞无明显区别。然而，稳定转染细胞的生长速度与对照细胞明显不同。在这里，我们表明反义VEGF可以成功地用于控制肿瘤生长，并可能提供抗血管生成的基因治疗。