黄芩苷诱导肿瘤细胞老化参与大肠癌治疗新机制研究

项目名称： 黄芩苷诱导肿瘤细胞老化参与大肠癌治疗新机制研究

项目编号： No.81472233

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 窦洁

作者单位： 中国药科大学

项目金额： 70万元

中文摘要： 诱导肿瘤细胞老化是近年肿瘤治疗研究新的方向和热点。在中药单体抗肿瘤活性及机制研究过程中，申请人首次发现来源于中药黄芩的单体--黄芩苷能够诱导人大肠癌细胞老化，同时其在体外有较强的抗大肠癌细胞活性。据此，本项目提出黄芩苷可通过诱导肿瘤细胞老化进行大肠癌治疗这一假设。本项目以细胞及动物模型为基础，拟从体内及体外进行以下的深入研究：①明确黄芩苷对大肠癌细胞老化的诱导作用及相关细胞调控机制；②探讨黄芩苷调节胞内信号蛋白，诱导肿瘤细胞老化的相关信号通路；③探讨黄芩苷诱导肿瘤细胞老化治疗大肠癌的体内疗效及其相应的细胞分子机制。本研究的结果将阐明黄芩苷诱导大肠癌细胞老化及细胞调控的机制，以及黄芩苷对大肠癌细胞的生长和发展进程的影响。该研究将为大肠癌的治疗提供新的方案和实验依据，也为中药单体治疗大肠癌的研发和临床应用开拓新思路。

中文关键词： C08_结；直肠肿瘤；大肠癌；黄芩苷；老化；机制

英文摘要： Induction of cancer cell senescence has recently been recognized as a novel strategy and new direction for cancer therapy. In our efforts to explore the anti-tumor efficacy and mechanisms mediated by traditional Chinese herb monomers, we first discovered that Baicalin, a monomer derived from the Chinese herb of Scutellaria baicalensis Georgi, can induce cell senescence of human colon cancer resulting in significant inhibition of tumor cell growth. Based on our preliminary studies, we hypothesized that Baicalin has a strong anti-tumor activity through the induction of tumor cell senescence, which could be used as a novel anti-tumor drug for colon cancer therapy. To test our hypothesis, we will perform the following three specific aims, using both in vitro in cell culture studies and in vivo in animal models. 1) Identify molecular mechanisms and cellular biological processes responsible for induction of cell senescence in colon cancer mediated by Baicalin; 2) Explore the molecular signaling pathways that control the molecular and biological alterations induced by Baicalin in human colon cancer cells leading to cancer cell senescence; 3) Investigate the therapeutic effect and related molecular mechanisms of senescence induction mediated by Baicalin in vivo in humanized colon cancer models. We anticipate that the studies we propose in this application will improve our fundamental understanding of the novel mechanisms and cellular processes of senescence induction mediated by Baicalin in human colon cancer cells that we have recently identified. Importantly, our proposed studies will allow us to explore the possibility of utilizing Baicalin as a new drug and an effective strategy for human colon cancer treatment, and will provide critical insights for the development of novel anti-tumor monomer drugs from Chinese herbs and for the clinical applications of traditional Chinese medicine as well.

英文关键词： C08-carcinoma of colon and rectrm;colon cancer;baicalin;senescence;mechanism