益气活血解毒中药化瘀丸通过肝素酶途径对血小板介导肿瘤细胞转移的干预作用研究

项目名称： 益气活血解毒中药化瘀丸通过肝素酶途径对血小板介导肿瘤细胞转移的干预作用研究

项目编号： No.81473643

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： 杨国旺

作者单位： 首都医科大学

项目金额： 74万元

中文摘要： 化瘀丸是郁仁存教授多年经验总结创制的益气活血解毒法肿瘤治疗有效方剂，前期研究表明其具有良好的抑制肺癌转移及调节凝血功能作用，可能与降低血小板异常活化有关。近年发现肝素酶高表达于血小板和肿瘤细胞，能降解硫酸乙酰肝素进而降解细胞外基质和基底膜，并通过干预血小板介导的肿瘤与内皮细胞粘附和血管生成促进肿瘤侵袭转移，是当前抗肿瘤研究的新热点和中医药抗肿瘤研究的新靶点。本课题拟进一步观察化瘀丸：①对Hpa-KO肝素酶敲除小鼠、Hpa-TG肝素酶高表达小鼠及正常小鼠肺癌生长转移的影响；②对不同肝素酶活性小鼠瘤组织和血小板肝素酶及其相关信号转导通路的影响；③对不同肝素酶活性荷瘤小鼠血小板功能及其相关肿瘤转移途径的的影响；④体外对不同转移能力肺癌细胞侵袭力、肝素酶表达及血小板、肿瘤与内皮细胞粘附的影响。以期从影响肝素酶含量和活性进而干预血小板介导的肿瘤转移角度阐释益气活血解毒法抗肿瘤的科学原理。

中文关键词： 益气活血解毒；肝素酶；血小板；肿瘤转移；中医药

英文摘要： Yiqihuoxuejiedu is the main principle for tumor treatment in traditional Chinese medicine, and HuaYuWan is one of the effective prescription based on this principle. Preliminary studies show that Huayuwan can be an effective measure for inhibiting the tumor metastasis and reducing the expression of platelet abnormal activation correlation factors in lewis lung cancer-bearing mice. Heparanase expresses at high level in platelet and tumor cells.Heparanase is known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix(ECM).It can also promote platelet mediated tumor cell metastasis by tumor-endothelial cell adhesion and angiogenesis pathways. In this study，we will explore the tumor inhibition effect of HuaYuWan prescription in heparanase-knockout transgenic mice (Hpa-KO),heparanase-over expressing transgenic mice (Hpa-TG) and controls(C57/BL6).We will also study in its intervention effects on heparanase expression in tumor tissue and platelet, heparanase-related signal transduction pathways and platelet function in different heparanase activity mice. In vitro experiments, we will study its intervention effects on cell invasiveness, heparanase expression and tumor-platelet -endothelial cell adhesion in different metastatic potential lung cancer cells. The results will further reveal the anti-tumor mechanism of the method of Yiqihuoxuejiedu and the scientific principles of compatibility of HuaYuWan prescription from the view of affecting the expression and activity of heparanase and platelet-associated tumor metastasis pathways.

英文关键词： Yiqihuoxuejiedu;heparanase;platelet;tumor metastasis;TCM