雄激素非依赖性前列腺癌细胞系功能性代谢物的鉴定及其信号通路研究

项目名称： 雄激素非依赖性前列腺癌细胞系功能性代谢物的鉴定及其信号通路研究

项目编号： No.81202026

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： 周武

作者单位： 温州医科大学

项目金额： 23万元

中文摘要： 前列腺癌是男性泌尿系最常见肿瘤之一，经内分泌治疗后易转化为雄激素非依赖性前列腺癌(AIPC)，给临床治疗带来困难，其转化机制已成为目前研究热点。本课题组前期研究以本实验室成功诱导培养的两株AIPC细胞株（实验组）和雄激素依赖性前列腺癌细胞株LNCaP（对照组）为研究对象，采用超高相液相色谱飞行质谱和气相色谱质谱技术对细胞内和培养上清液的代谢物进行检测，发现并鉴定了23种候选差异代谢物。本课题组拟进一步通过生物信息学数据库对部分候选差异代谢物进行分析，寻找候选差异代谢物的代谢途径中关键酶；采用分子生物学技术调节关键酶基因的表达，通过检测细胞侵袭力和靶代谢物水平等指标的变化，鉴定AIPC转变过程中功能性代谢物并分析其信号传导途径。本课题研究有望发现AIPC转化过程中关键性的代谢物质及其细胞信号通路，为进一步深入研究AIPC发生机制提供实验基础。

中文关键词： 前列腺癌；雄激素非依赖性；代谢组学；信号通路；

英文摘要： Prostate cancer is the most commonly diagnosed malignancy in uropoiesis system and easy conver to androgen independent prostate cancer(AIPC) after endocrine therapy,which make these changes happened became the hot spot in recently reasch.We found 23 different metabolin between ACPI cell(experimental group) and androgen-dependent prostate cancer cell LNCaP(control group)in cytoplasm and metabolin within supernatant fluid which was selceted after the cell cultivantion used UPLC-Q-TOF-MS andgaschromatographic mass spectrometry(GCMS).In this study,we plan to analyze this 23 different metabolin through bioinformatics way to find out the key enzyme in disparity metabolic pathway,then regulate the gene expression of the key enzyme through molecular biology technology.In the same time, we plan to identificate the key metabolin and it cellular signal transduction pathway in the AIPC transition process of LNCaP, by deteceting the cell invasiveness and the target metabolin level after cell transfection and siRNA-mediated interference. In this topic, it maybe could to realize the key metabolin in the LNCaP cell convert to AIPC precess and offer further experiment foundation for AIPC development mechanisms study.

英文关键词： prostatic cancer；androgen independent；metabonomics；signal pathway；