丹参酚酸/丹参酮类对血小板介导肿瘤血行转移的整合效应研究

活血化瘀药丹参抗血栓作用明确，在心血管疾病中广泛应用，抗癌方中应用频度也很高，课题组前期实验证实丹参对肿瘤血管生成和转移有抑制作用，且脂溶性丹参酮类和水溶性丹酚酸类作用靶点不同。纵观文献可知，肿瘤发生血行转移关键环节是血小板功能被恶性肿瘤劫持，从而介导癌栓形成和肿瘤血管生成。而癌栓形成机制与血栓相似，均由异常活化血小板介导，因此课题组提出丹参通过两组分组合对血行转移产生整合效应的假说。拟提取丹参活性成分天然配比A、丹酚酸类B、丹参酮类C，利用选择性成分敲除策略获得A-B和A-C，采用析因设计结合酶联免疫、Western Blot、Realtime PCR、质粒稳转表达分析等技术，确认丹参酚酸类和丹参酮类对血小板介导肿瘤血行转移中关键环节（血小板活化、聚集，肿瘤细胞黏附、迁移、肿瘤血管生成）的影响，应用数学药理学的方法分析两组分组合是否产生大于加和的协同作用，从新的视角为临床应用丹参提供支撑

As a Chinese Medicine which promoting blood circulation and removing blood stasis, Salvia has an identified antithrombotic effect and was widely used in cardiovascular disease. Its application of frequency in TCM anticancer prescription is also high. Our team had confirmed that salvia can inhibit tumor angiogenesis and metastasis in previous experiments, in addition the hydrophilic phenolic acids and the lipophilic tanshinones have different targets. The review literature shows that the key step of tumor hematogenous metastasis is that platelet functions are hijacked by malignant tumors, which mediate emboli formation and tumor angiogenesis. The mechanism of tumor emboli formation is similar to thrombus formation. Both of them are mediated by abnormal activated platelet. So we give a hypothesis that the active ingredient groups of salvia have an integration effect on tumor hematogenous metastasis. The active ingredient of salvia including natural ratio (A)、phenolic acids (B) and tanshinones (C) will be extracted. (A-B) or (A-C) will be got by the strategy of selective component knockout. The modern techniques such as factorial design combined with ELISA, Western Blot, Realtime PCR, plasmid stability expression analysis technology will be used to confirm how Salvianolic acid and tanshinone have an effect on the key step of tumor hematogenous metastasis mediated by platelet (platelet activity and aggregation, tumor cells adhesion and migration, tumor angiogenesis). Methods of mathematical pharmacology will be applied to analyze whether the synergistic effect of combining two parts components is bigger than simple sum of them. This project provides a support for clinical application of salvia from a new perspective.