VEGF介导MEK/ERK信号通路调控大肠癌侵袭转移以及益气复生方对其作用的研究

项目名称： VEGF介导MEK/ERK信号通路调控大肠癌侵袭转移以及益气复生方对其作用的研究

项目编号： No.81460704

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邓皖利

作者单位： 新疆医科大学

项目金额： 47万元

中文摘要： 大肠癌的复发转移是造成大肠癌治疗失败的主要原因之一。癌细胞发生侵袭迁移是多因素、多机制参与的结果，涉及多种信号转导活性的改变。现已证实，ERK通路的激活可以诱发肿瘤侵袭转移的发生，但是ERK通路的激活过程目前尚未明确。前期研究发现VEGF可以使MEK发生磷酸化激活ERK通路，诱导肠癌侵袭转移；益气复生方能抑制肠癌细胞的迁徙转移能力，下调MEK/ERK磷酸化表达。因此，我们推测VEGF激活MEK信号通路可能是肿瘤发生侵袭转移的机制之一。本研究通过收集临床肠癌复发转移标本，建立裸鼠人肠癌移植瘤转移模型，采用细胞划痕实验、Western blot等实验技术，进行临床组织标本、体内动物转移模型、体外细胞实验研究，探讨益气复生方对VEGF介导的ERK信号通路的调控机制。揭示中药抗肠癌侵袭转移的机制，为中医药防治肠癌复发转移提供科学依据。

中文关键词： 益气复生方；MEK/ERK信号通路；VEGF；大肠癌；侵袭转移

英文摘要： Recurrence of cancer is one of the main failure causes in colorectal cancer treatment. Migration and invasion of cancer cells is the result of many mechanisms and factors, which involving a variety of signal transduction activity. It has been proved that the activation of ERK pathway can induce invasion and metastasis in tumor, however, the underlying mechanism remains unknown. Our previous studies showed that VEGF induced activity of ERK signal transduction, which was associated with an enhanced phosphorylation of MEK. We also found that Yi-Qi-Fu-Sheng herbal formula could inhibit invasion/metastasis and the level of phosphorylation of MEK/ERK. Based on previous studies, we speculate that activation of VEGF in invasion and metastasis via MEK signaling pathway may be one mechanism of colorectal cancer. In this study, some experimental techniques will be used to explore the mechanism of recurrence and metastasis in colorectal cancer, such as collecting clinical specimens, establishing human colorectal cancer nude mice xenograft metastasis model, Western blot and other experimental techniques. We will investigate the effects of Yi-Qi-Fu-Sheng formula on VEGF/MEK/ERK signaling in colorectal cancer from clinical, in vitro and in vivo aspects. It will be helpful to find the target in the prevention and treatment of migration and invasion.

英文关键词： Yi-Qi-Fu-Sheng formula;MEK/ERK signaling pathway;VEGF;Colorectal cancer;invasion and metastasis