PEDF通过促进肺癌血管正常化增强放射治疗作用及分子机制研究

项目名称： PEDF通过促进肺癌血管正常化增强放射治疗作用及分子机制研究

项目编号： No.81201736

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 徐祖敏

作者单位： 广东医学院

项目金额： 23万元

中文摘要： 以往研究证实PEDF可通过抑制肿瘤血管新生抑制肿瘤的生长，但PEDF对肿瘤血管正常化的作用尚无报道。我们的预实验表明PEDF可诱导小鼠肺癌移植瘤血管正常化。RGS5是调控肿瘤血管正常化的重要因子，其表达具有低氧依赖性，受HIF-1α调控。我们前期研究表明PEDF可下调HIF-1α，且在肺癌血管正常化期间，RGS5的表达下降，提示PEDF可能通过HIF-1α调控RGS5进而调控肿瘤血管正常化。诱导血管正常化是血管新生抑制因子增强放疗抗肿瘤作用的重要机制，我们推测PEDF可提高放疗对肺癌的治疗作用。本项目拟观察：PEDF促进肺癌血管正常化的作用并初步探讨其分子机制，明确PEDF促进肺癌血管正常化的时间窗，探讨PEDF联合放疗对肺癌的最佳治疗模式，旨在为肺癌等恶性肿瘤治疗提供新的候选药物及为临床应用提供科学依据和理论基础。

中文关键词： 色素上皮衍生因子；肺癌；G蛋白信号通路调节蛋白5；血管正常化；放射治疗

英文摘要： Over the past decade, a host of studies have shown that pigment epithelium derived factor (PEDF) could inhibit the angiogenesis and growth of several types of cancers，including lung cancer. However, the effects of PEDF on tumor vascular normalization remains unknown. Our previous study showed that during PEDF treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Accordingly, the aim of the project is to investigate the anti-tumor growth effects of PEDF combined with radiotherapy. Furthermore, the mechanism by which PEDF induces vasulcar normalization will be explored. Regulator of G protein 5 (RGS5) was discovered as one of the factors modulated tumor vascular normalization, which is regulated by hypoxia-induced factor 1alpha (HIF-1α). Downregulating of RGS5 induces tumor vessel normalization. Interestingly, our and the others' studies demonstrated that the activity of HIF-1α were inhibited by PEDF. Therefore, we proposed that PEDF might induce vascular normalization by downregulating RGS5 expression via HIF-1α. In summary, the present study focus on the effects and the potential mechanisms of PEDF on tumor vascular normalization in a xenografted model of lung cancer. We aimed to e

英文关键词： pigment epithelium derived factor；lung cancer；regulator of G-protein signaling；vascular normalization；radiation therapy