ACE2-Ang(1-7)-Mas轴对获得性铂类耐药肺癌血管生成的影响及机制研究

项目名称： ACE2-Ang(1-7)-Mas轴对获得性铂类耐药肺癌血管生成的影响及机制研究

项目编号： No.81201837

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： 冯耘

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 近年来获得性铂类耐药肿瘤的血管生成研究逐渐成为肿瘤耐药的研究热点。新近在膀胱癌的研究发现肿瘤局部肾素血管紧张素系统(RAS)中ACE-AngⅡ-AT1受体轴可促进耐铂类药物肿瘤VEGF的产生，而与该轴对抗的RAS新分支ACE2-Ang(1-7)-Mas轴是否能降低耐药肿瘤VEGF的生成，从而抑制血管生成，逆转肿瘤耐药还尚未见研究报道。我们近几年来一直致力于ACE2-Ang(1-7)-Mas轴在肺癌中作用的研究，发表多篇相关文章。最近我们研究发现耐铂类药物肺癌VEGF及血管生成增加，肿瘤局部RAS系统组分失衡，并构建了稳定过表达ACE2的耐顺铂肺癌细胞株。本研究拟在我们现有研究基础上，通过探讨该新分支在耐药肺癌VEGF生成的作用，并寻找相关的作用通路，从分子、细胞及动物整体水平揭示该新分支与耐铂类药物肺癌血管生成的关系，为进一步研究耐药肺癌的分子生物学特征，寻找逆转肺癌耐药的药物提供新的方向

中文关键词： 非小细胞肺癌；血管生成；获得性铂类耐药；ACE2-Ang(1-7)-Mas轴；

英文摘要： Tumour angiogenesis of acquired platinum resistance has become a hot spot in the field of tumor resistance. It is recently reported that the ACE-Ang II-AT1 receptor axis in local renin-angiotensin system (RAS) plays a pivotal role in the production of vascular endothelial growth factor (VEGF). As evidenced, ACE2-Ang(1-7)-Mas axis, as the new branch of RAS, has the antagonism against ACE-Ang II-AT1 receptor axis. However, effect and mechanism of this new branch in the tumour angiogenesis of acquired platinum resistance in lung cancer still remains unclear. We recently have studied the effect of ACE2-Ang(1-7)-Mas axis in lung cancer and published some relevant articles. Our results convincingly demonstrated that VEGF is increasingly expressed and the local RAS is imbalanced after the development of acquired platinum resistance in lung cancer. We also established acquired platinum resistance lung cancer sublines with overexpressed ACE2. Based on previous studies, we in this study aim to investigate the role and mechanism of ACE2-Ang(1-7)-Mas axis in the VEGF production and tumor angiogenesis after the development of acquired platinum resistance, and further to establish whether the new branch could suppress the growth of platinum resistance lung cancer. For practical reasons, we hope that this study will provide th

英文关键词： NSCLC；tumour angiogenesis；acquired platinum resistance；ACE2-Ang(1-7)-Mas axis;；