Periostin-avβ3-FAK-PI3K通路在褐藻糖胶抗乳腺癌转移中的作用机制研究

项目名称： Periostin-avβ3-FAK-PI3K通路在褐藻糖胶抗乳腺癌转移中的作用机制研究

项目编号： No.81502298

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 薛美兰

作者单位： 青岛大学

项目金额： 17万元

中文摘要： 三阴性乳腺癌恶性程度高、侵袭性强，对内分泌及靶向治疗的效果均欠佳。褐藻糖胶（Fucoidan）是从海带中提取纯化的天然活性分子。申请者前期研究证实Fucoidan能减少乳腺癌组织内新生血管，抑制其肺转移。在乳腺癌的转移中起重要作用的Periostin蛋白通过αvβ3-FAK-PI3K信号通路调控肿瘤细胞的增殖、凋亡及血管生成，而我们前期检测的survivin、bcl-2、cyclinD1等均是该通路的下游靶基因，据此推测Fucoidan可能通过该通路抗乳腺癌转移，但还缺乏实验依据。本项目拟利用三阴性乳腺癌细胞系和动物模型明确Fucoidan抗乳腺癌转移的分子作用，探讨其对Periostin-αvβ3-FAK-PI3K通路的影响，并应用siRNA和通路抑制剂下调通路进行验证；采用亲和标记法结合蛋白飞行质谱技术探究其作用靶点，筛选膜上受体,为Fucoidan抗乳腺癌转移的分子机制提供实验依据。

中文关键词： 褐藻糖胶；三阴性乳腺癌；Periostin蛋白；肿瘤转移；受体筛选

英文摘要： The malignance and invasiveness of triple-negative breast cancer is high, the prognosis is poor. The effect of endocrine and target therapy was poor. There is very necessary to find a natural active drug with less toxicity. Fucoidan is a complex sulfated polysaccharide that is found in brown algae. Recently, the diverse biological activities of fucoidan have been studied intensively. In particular, the antitumor activity has recently attracted considerable attention. Our recent studies have demonstrated that fucoidan has an anti-tumor effect on breast cancer（Plos One，2012; Nutrition and Cancer, 2013）. We found that fucoidan could strongly inhibit the metastatic of breast cancer, and this effect might be related to the Periostin-αvβ3-FAK-PI3K pathway. The goal of this experiment is to investigate the effect and mechanism of fucoidan on the metastatic of MDA-MB-231 breast cancer in vivo and in vitro. The signal molecules involved in Periostin-αvβ3-FAK-PI3K pathway are analyzed by fluorescence quantity RT-PCR and Western Blot. The siRNA and FAK inhibitor will be applied to determine the effect of fucoidan on Periostin-αvβ3-FAK-PI3K pathway. The targeting molecules of fucoidan will be further identified by the affinity labeling and proteins flight mass spectrometry technology. Thereby, the study may determine the molecular mechanism of anti-tumor activity of fucoidan and provide theory and experimental evidence for prevent and therapy of fucoidan on breast cancer.

英文关键词： fucoidan;triple-negative breast cancer;Periostin;Tumor metastasis;Receptor selection