瞬时受体电位M8在前列腺癌骨转移中作用及其机制的研究

项目名称： 瞬时受体电位M8在前列腺癌骨转移中作用及其机制的研究

项目编号： No.81202027

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： 杨中华

作者单位： 武汉大学

项目金额： 23万元

中文摘要： 约80%前列腺癌患者最终会出现骨转移并死于骨相关事件。目前治疗骨转移药物大多因作用机制缺乏特异性可引起严重的副作用，探索新的靶向治疗方法已成当务之急。瞬时受体电位M8（TRPM8）是新近发现的前列腺特异性钙通道，申请人前期研究表明TRPM8通过调节细胞内Ca2+稳态而调控前列腺癌细胞增殖及迁移，可作为肿瘤治疗的新靶点。最新的研究表明TRPM8及其激动剂PSA参与前列腺癌骨转移调控，我们推测其与PSA激活TRPM8相关。本课题拟在前期基础上，采用基因调控及使用TRPM8通道激动剂和（或）阻断剂的方法，结合荷瘤裸鼠动物模型，揭示TRPM8对前列腺癌细胞与骨微环境相互作用的影响及TRPM8在成骨/破骨细胞定向趋化前列腺癌细胞中的作用。通过体内、体外实验相结合，探讨通过TRPM8这一靶点干预前列腺癌与骨微环境之间"恶性循环"，从而抑制前列腺癌骨转移的可能性，为前列腺癌的基因靶向治疗奠定理论基础。

中文关键词： 前列腺癌；骨转移；瞬时受体电位；离子通道；微环境

英文摘要： Prostate cancer will causes bone metastasis and skeletal-related events (SRE) in about 80% patients for which there is no satisfactory treatment. For lack of specifity, current pharmaceuticals may cause serious side-effects. So it is crucial to explore novel targeted therapy. As an important second massager, Ca2+ plays an important role in regulation of cell proliferation, differentiation, migration and invasion and has been a new target in cancer therapy. Transient receptor potential M8 (TRPM8) is an ion channel specifically expressed in prostate and play important role in regulation Ca2+ homostasis. Our previous studies demonstrated that TRPM8 regulated the proliferation and migration of prostate cancer cells both in vitro and in vivo, while latest study showed that TRPM8 and its natural agonist PSA played a crisis role in regulating bone metastasis of prostate cancer which maybe caused by the activation of PSA-TRPM8 pathway. Based on our previous results, we will, by using agonist and/or antagonist through coculture (in vitro) and athymic nude mice model (in vivo), explore the role of TRPM8 in the interaction of prostate cancer cells and bony microenvironment, namely, prostate cancer cells inducing differentiation and activation osteoblast and osteoclast, while osteoblast and osteoclast chemotaxis prostate ca

英文关键词： prostate cancer；bone metastasis；transient receptor potiential；ion channel；microenvironment