抑癌方对ROS/HIF-1α途径调控血管拟态促进大肠癌侵袭转移的干预

项目名称： 抑癌方对ROS/HIF-1α途径调控血管拟态促进大肠癌侵袭转移的干预

项目编号： No.81473624

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： 侯风刚

作者单位： 上海中医药大学

项目金额： 72万元

中文摘要： 大肠癌侵袭转移，是其相关死亡的主要原因。血管拟态（VM）在其中扮演着关键角色，ROS/HIF-1α途径是VM的主要调控机制。目前尚无有效的肿瘤VM治疗方法，也未见中药干预大肠癌VM形成的文献报道。 抑癌方在大肠癌侵袭转移上有确切疗效，我们前期研究表明，这与抑制VM形成有关，但具体机制不明。我们还发现，该方能下调小鼠移植瘤内ROS/HIF-1α途径上的HIF-1α和VEGF水平、减少MMP2表达，体外研究能降低MMP2活性。因此，提出干预ROS/HIF-1α途径调控VM形成是该方抗大肠癌侵袭转移的机制。 本项目拟研究：1）验证ROS/HIF-1α途径调控VM形成促进大肠癌侵袭转移的作用；2）通过体内外实验，重点研究该途径上是哪些分子介导抑癌方发挥抑制大肠癌VM形成和侵袭转移的作用。预期结果不仅有助于明确其作用机制，也为中医药通过抑制VM治疗大肠癌侵袭转移提供理论支持和实验依据。

中文关键词： 中医药；大肠癌；血管拟态；侵袭转移；信号通路

英文摘要： Invasion and metastasis of colorectal cancer is the leading cause of death related. Vascular Mimicry (VM) play a key role in the course and ROS/HIF-1α pathway is its main regulatory mechanisms. Currently there is neither mature and effective treatment for tumour VM, nor any report about intervention of Chinese herbs on VM formation of colorectal cancer. Yiaifang can effectively treat invasion and metastasis of colorectal cancer and our preliminary studies indicate the treatment is closely related to the fact that it can significantly inhibit VM formation, but the specific mechanism is still unknown. We also found that the herb compound can reduce the level of HIF-1α、VEGF and MMP2 of ROS/HIF-1α pathway in mouse xenograft and let down the activity of MMP2 in vitro. Therefore, we propose that its intervention on the course of ROS/HIF-1αpathway regulating VM formation is the mechanism of its anti-invasion and metastasis of colorectal cancer. On the base of validating the fact that ROS/HIF-1α pathways can regulate the formation of VM and then promote the invasion and metastasis of colorectal cancer,the project intends to focus on which molecules of ROS/HIF-1α pathways can mediate its effection on the VM formation and invasion and metastasis of colorectal cancer. The expected results will be able to not only clarify its mechanism, but also provide theoretical support and experimental evidence for Chinese herb treating colorectal cancer invasion and metastasis via inhibiting VM formation.

英文关键词： Chinese herb;Colorectal cancer;Vascular mimicry;Metastasis;Signal pathway