PEDF诱导视网膜母细胞瘤凋亡的作用及分子机制

项目名称： PEDF诱导视网膜母细胞瘤凋亡的作用及分子机制

项目编号： No.81001014

项目类型： 青年科学基金项目

立项/批准年度： 2011

项目学科： 金属学与金属工艺

项目作者： 程锐

作者单位： 中山大学

项目金额： 10万元

中文摘要： 申请人发现血管新生抑制因子PEDF抑制视网膜母细胞瘤（Rb）血管新生和肿瘤生长；最近又发现高剂量PEDF可诱导Rb细胞凋亡；提示PEDF可能通过直接诱导Rb细胞凋亡和抑制血管新生的双重作用协同抑制Rb生长，但PEDF诱导Rb细胞凋亡的分子机制尚不明确。预实验结果表明PEDF上调Rb细胞中FasL并促进caspase8切割，提示PEDF可能通过Fas/FasL途径诱导Rb细胞凋亡。PPARγ26159;FasL新的转录因子，介导PEDF诱导血管内皮细胞凋亡；MAPK是调控PPARγ30340;关键分子；本项目拟明确PEDF是否通过MAPK-PPARγasL-caspase8信号通路诱导Rb细胞凋亡。PEDF受体LR和ATGL分别介导其抑制血管新生和神经元保护功能，本项目拟进一步明确PEDF诱导Rb细胞凋亡作用的受体，旨在阐明PEDF诱导Rb细胞凋亡的信号机制，为治疗视网膜母细胞瘤提供新的候选药物和理论依据。

中文关键词： PEDF；视网膜母细胞瘤；凋亡；PPAR；受体

英文摘要： We have previously shown that anti-angiogenic inhibitor PEDF suppresses neovascularization and tumor growth of retinoblastoma(Rb). Our recent studies have shown that high concentration of PEDF induced the apoptosis of retinoblastoma cells, which suggested that PEDF suppressed tumor growth of retinoblastoma by directly inducing apoptosis of Rb cells and indirectly inhibiting angiogenesis of tumor tissues. However, the mechanism of PEDF on apoptosis of Rb cells has not been clarified. Recently, our preliminary results showed that PEDF up-regulated FasL levels and promoted cleavage of caspase8 in Rb cells. PPARγs a new-found transcription factor of FasL, which was identified to mediate PEDF inducing apoptosis of vascular endothelial cells. The present study was designed to explore whether PEDF activated PPARγasL-caspase8 to induce apoptosis of retinoblastoma. This study aims to clarify the signal transduction mechanism of PEDF on apoptosis of retinoblastoma cells, and will give an insight to look for a new candidatd drug with potent anti-retinoblastoma activities

英文关键词： PEDF;retinoblastoma;apoptosis;PPAR