Antisense VEGF Tumor Gene Therapy for Malignant Gliomas (Anti-angiogenic Gene Therapy)

随着肿瘤体积的增大，肿瘤不断依赖功能良好的血管系统来保证氧气和营养物质的供应。血管内皮生长因子不仅是发育过程中的关键介质，也是缺氧和肿瘤诱导的血管生成的关键介质。以抑制肿瘤血管生成为目的的反义血管内皮生长因子基因治疗可能是治疗高血管和侵袭性恶性胶质瘤的一种成功策略。我们研究了阻断血管内皮生长因子/血管内皮生长因子受体旁分泌环路是否会抑制肿瘤血管生成。采用反义血管内皮生长因子、血管内皮祖细胞、HIF-1诱骗、siRNA等策略阻断该通路。逆转录病毒载体导入的反义血管内皮生长因子可显著抑制血管生成，抑制肿瘤生长，延长生存期，且无严重不良反应。因此，我们的研究支持抗血管生成肿瘤治疗是治疗恶性胶质瘤的一种有前途的治疗方法。

With increasing size tumors are continually dependent on functional blood vessel system to guarantee the supply with oxygen and nutrients. VEGF is a key mediator not only of developmental but also of hypoxia-mediated and tumor-induced angiogenesis. Gene therapy using antisense VEGF with the aim to inhibit tumor angiogenesis may be a successful strategy for the treatment of highly vascular and invasive malignant gliomas. We investigated whether the blockage of VEGF/VEGFR paracrine loop may inhibit the tumor-angiogenesis. Several strategies, such as antisense VEGF, endothelial progenitor cells, HIF-1 decoy, siRNA, were adopted to block this pathway. Antisense VEGF introduced by retrovirus vectors showed a significant inhibition of VEGF expression, angiogenesis, tumor growth and prolongation of survival time without any serious adverse effects. Therefore, our study supports the concept that anti-angiogenic tumor therapy is a promising therapy for malignant gliomas.