海姆泊芬光动力诱导氧化磷脂对细胞自噬及死亡的作用

项目名称： 海姆泊芬光动力诱导氧化磷脂对细胞自噬及死亡的作用

项目编号： No.81472898

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 赵邑

作者单位： 北京大学

项目金额： 70万元

中文摘要： 光动力治疗（PDT）是肿瘤治疗的新选择，新型光敏剂（PS）海姆泊芬是我国研发的国家一类新药。PDT效应和其引起的细胞死亡密切相关。在PDT中，PS在光源照射下产生的ROS可以诱导自噬等细胞效应。实验证明自噬和凋亡和坏死之间有复杂的相互作用。在前期研究中，我们首先发现UVA可诱导细胞产生氧化磷脂（OxPLs），后者可以显著诱导自噬，并证明自噬是OxPLs的重要细胞内处理途径。在预实验中，我们初步证实海姆泊芬PDT（hPDT）可以诱导细胞产生氧化反应及OxPLs。因此假设：hPDT可通过诱导细胞OxPLs而诱导细胞自噬，进而对细胞死亡产生重要影响；通过对OxPLs及自噬的调控可能对hPDT的效应产生重要影响。本研究拟从hPDT对血管内皮细胞的OxPLs诱导效应入手，研究OxPLs对细胞自噬及死亡的影响及其调控机制。可能进一步明确PDT作用的分子机制，为提高PDT疗效开发新的药物靶点。

中文关键词： 光动力疗法；自噬；细胞凋亡；氧化磷脂

英文摘要： Photodynamic therapy (PDT) is a new option for tumor treatment. Hemoporfin is a new photosensitizer (PS) developed in China. The effect of PDT is largely dependent on its ability to induce cell death. In PDT, PS can induce ROS production after exposure to appropriated light source. ROS has been proven to be able to induce autophagy, which has be shown to have significant effect on apoptosis and necrosis. It's of great importance for improving the efficacy of PDT to understand the feature and mechanism of the interaction among the autophagy, apoptosis and necrosis, and their impact on tumor response to PDT. In our previous studies, we have shown that UVA can induce cellular oxidized phospholipids (OxPLs), which can further induce autophagy, and the latter is an important pathway for OxPLs metabolism in cells . In preliminary studies, we also detected that OxPLs might be involved in the effect of hemoporfin-PDT (hPDT). Thus we hypothesized that: a) hPDT induced OxPLs might induce autophagy, which might affect cell death. b) blocking or enhancing the OxPLs-autophagy pathway might affect cellular or tissue response to hPDT. In this program, we proposed to study the hPDT induced OxPLs-autophagy pathway and its effect on cell death. This study might lead to deeper understanding of molecular mechanism of PDT and further possibility of discovering new target to improve PDT effect.

英文关键词： photodynamic therapy;autophagy;apoptosis;oxidized phospholipids