CD147参与AR调控雄激素非依赖性前列腺癌的作用及机制研究

项目名称： CD147参与AR调控雄激素非依赖性前列腺癌的作用及机制研究

项目编号： No.81202031

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： 方芳

作者单位： 吉林医药学院

项目金额： 23万元

中文摘要： 雄激素非依赖性前列腺癌(AIPC)是前列腺癌病程中的致死性阶段，目前无法治愈。AIPC发生与雄激素受体(AR)密切相关。我们研究发现，CD147与AIPC侵袭和转移相关；AIPC发生过程中CD147和细胞核内AR共激活因子β-catenin表达水平升高，但CD147的作用尚不清楚。新近研究证实，肺癌中CD147能促进β-catenin的细胞核内水平，导致癌细胞增殖和侵袭。因此，我们首次提出假说：CD147表达升高上调细胞核内β-catenin水平，继而促进AR表达和活化，导致AIPC发生。本研究拟采用分子生物学、细胞生物学和免疫学等技术，在细胞和分子水平上检测CD147、β-catenin和AR的相互作用，阐明CD147正向参与AR调控AIPC发生的作用和机制。采用公认的荷瘤裸鼠去势模型，在体内水平进一步验证。本项目旨在深入探讨AIPC的发病机制，为临床治疗提供新的理论依据和药物靶点。

中文关键词： CD147；PI3K/Akt；前列腺癌；胡桃醌；抗肿瘤

英文摘要： Androgen-independent prostate cancer (AIPC) is the lethal stage of prostate cancer, for which there is no curative therapy. Androgen receptor (AR) plays a central role in the development of AIPC. We find out that CD147 is associated with the invasion and migration of AIPC. The nuclear fractions for up-expression CD147 cells also contained a increased level of the β-catenin that is a AR co-activator in process of AIPC. But the functions of CD147 are not clear. A recent study confirms that the CD147 in lung cancer cells can elevate the level of β-catenin in the nucleus and promote the proliferation and invasion of cells. Therefore, we, for the first time, propose the hypothesis: up-regulated expression of CD147 could increase the level of β-catenin in the nucleus and then promote the AR expression and activation, which results in AIPC occurence. In this study, we detect the interaction of CD147, β-catenin and AR in the cellular and molecular level and clarify the functions and mechanisms of CD147 which positively participate in the AR regulated AIPC by technology of molecular biology, cell biology and immunology methods. The tumor xenograft model mouse with castration is adopted to testify the role of CD147. The aim of our study is to explore the pathogenesis of AIPC and provide the new theoretical basis and drug

英文关键词： CD147；PI3K/Akt；prostate cancer；Juglone；anticancer