caveolin-1 在紫杉醇诱导的肺癌多药耐药及侵袭转移中的分子机制研究

项目名称： caveolin-1 在紫杉醇诱导的肺癌多药耐药及侵袭转移中的分子机制研究

项目编号： No.81201838

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2

项目作者： 韩非

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 肺癌是我国高发且死亡率极高的恶性肿瘤之一，化学治疗在肺癌的综合治疗中占据着重要地位，然而多药耐药是困扰肺癌化疗疗效的一个重要原因。近年来的研究发现化疗不仅导致肿瘤耐受，还会引起肿瘤侵袭转移能力的改变。但肿瘤的多药耐药与侵袭转移的内在联系还不清楚。Caveolin-1是近年发现的与肿瘤多药耐药密切相关的一个新基因，然而caveolin-1在参与紫杉醇诱导的肺癌多药耐药形成及侵袭转移中的作用及其机制还不得而知。本项目通过细胞学和动物学实验体内外研究caveolin-1在紫杉醇诱导的肺癌耐药中作用及调控P-gp、MRP的分子机制，研究caveolin-1在紫杉醇诱导的耐药细胞侵袭转移中的作用，从EGFR通路及细胞EMT两方面探讨其机理，分析caveolin-1介导的EMT是否是肿瘤耐药与侵袭转移的内在联系机制之一，这些研究为进一步阐明肺癌多药耐药及侵袭转移的发生机制提供一定的理论基础及实验依据。

中文关键词： Caveolin-1；紫杉醇；多药耐药；侵袭转移；凋亡

英文摘要： Lung cancer is the most common cancer death cause in the world, chemotherapy has played an important role in the compositive treatments of lung cancer,but the multidrug resistance of tumor has been an obstacle in chemotherapy of lung cancer.Recent studies showed chemotherapy not only leaded to tumor resistance, but also caused tumor metastasis. However, the intrinsic relationship beteen tumor multidrug and metastasis has been not clarified. Caveolin-1 was found as a new gene in tumor multidrug resistance recently, but the effect and mechanism of caveolin-1 in lung cancer multidrug resistance and metastasis have not been investigated until now.In this study, we use cell and animal models, investigate the mechanism of caveolin-1 regulating P-gp, MRP and metastasis in paclitaxel induced lung cancer multidrug resistance in vivo and vitro.Futhermore,whether tumor multidrug resistance and metastasis is related with cell Epithelial-Mesenchymal Transition, also is investigated. These studies will provide the necessary academic foundation and test proofs for molecular mechanism elucidation of lung cancer multidrug resistance and metastasis and reversion of lung cancer multidrug resistance.

英文关键词： Caveolin-1；Paclitaxel；Multidrug resistance；Invasion and metastasis；Apoptosis