钙池调控钙内流对丁酸钠诱导大肠癌细胞凋亡调控机制的研究

项目名称： 钙池调控钙内流对丁酸钠诱导大肠癌细胞凋亡调控机制的研究

项目编号： No.81202204

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 孙素霞

作者单位： 南方医科大学

项目金额： 23万元

中文摘要： 丁酸钠（sodium butyrate,NaB）作为膳食纤维在肠道内的代谢产物之一，可诱导大肠癌等多种肿瘤细胞凋亡。钙池调控钙内流(Store-operated Ca2+ entry, SOCE)是指内质网中Ca2+浓度下降诱发细胞外Ca2+内流过程，可调控细胞生长、凋亡等功能。本研究的前期结果提示，SOCE 在NaB促大肠癌细胞凋亡过程中发挥一定作用，但其具体机制不明。本研究拟通过体外实验，如RNAi、质粒转染、Ca2+成像技术等方法，探讨改变SOCE 活性对大肠癌细胞凋亡率和细胞内游离Ca2+浓度影响，以及NaB 对STIM1、Orai1、Calpain、Caspase 等活性影响；进而通过体内裸鼠成瘤试验研究调节SOCE 活性对NaB 体内抗肿瘤活性的影响。项目目标是明确SOCE 在NaB 促大肠癌细胞凋亡中的作用机制，为临床上开发NaB 为大肠癌的治疗药物提供科学的理论依据。

中文关键词： 丁酸钠；大肠癌；细胞凋亡；钙离子；钙池调控钙内流

英文摘要： Sodium butyrate (NaB) as one of the end products of dietary fiber induces apoptosis in various types of cancer cells, including colorectal cancer, breast cancer cells. However, the mechanism of action remains unclear. store-operated Ca2+ entry（SOCE) refers to the phenomenon that depletion of intracellular Ca2+ stores activates Ca2+ channels in the plasmamembrane as a compensatory mechanism to refill the internal Ca2+ store. Previous studies have suggested that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. however, the exact mechanism have not yet been elucidated comprehensively. The purpose of this study is to explore the effect of change SOCE activity on apoptosis rate and intracellular free Ca2+ concentration in vitro experiments, such as RNA interference，plasmid transfection, Ca2+ imaging, and the effect of NaB on activity of STIM1, Orai1, Calpain, caspase. And then study the effect of NaB on SOCE and in vivo tumorigenicity of nude mice. The purpose of this study is understand the molecular pathogenesis of NaB-induced apoptosis in colorectal cancer cells, and provide scientific and theoretical basis for the clinical development of NaB treatment of colorectal cancer drugs.

英文关键词： sodium butyrate；colorectal cancer；cell apoptosis；calcium；store-operated calcium entry