课题组自2003年以来在国家自然基金项目滚动支持下，阐明活血化瘀中药对肿瘤转移是促进还是抑制取得重要进展。新近发现“癌栓”形成与“免疫逃逸”是肿瘤血行转移最为重要的环节，在活血化瘀药存在系列芳香酸类成分通过抑制COX-2从而抑制癌栓形成的基础上，发现活血化瘀药中还存在一类可抑制PD-L1非芳香酸类成分。结合物种间协同进化理论，提出COX-2与PD-L1对循环肿瘤细胞免疫逃逸的协同作用可能是活血化瘀药多成分多靶抑制肿瘤血行转移更为重要的机制。为完成以上假说，课题组构建可视、动态、灵敏的计算生物学肿瘤血行转移体内模型，结合构建人源化修饰的MC38-hPDL1工程细胞株及C57BL/6背景的PD-1人源化小鼠模型，利用定量药理学的方法，将分子、细胞均回归整体，从整体观的角度多层次揭示活血化瘀法（药）多成分多靶抑制肿瘤血行转移的整体协同机制，为治则治法研究提供可借鉴的思路和方法。

Since 2003, with the continuous support from National Natural Science Foundation of China, our group has been studying on the roles of blood activating and stasis resolving Chinese medicine in cancer metastasis and has achieved important progress in studying their roles of either promoting or inhibiting metastasis. Recently, there are discoveries showing "cancer-associated thrombosis" and "immune escape" are the most important events in tumor blood metastasis. We have found that a series of aromatic acid components inhibit cancer-associated thrombosis by inhibiting COX-2 in blood activating and stasis resolving Chinese medicine. Meanwhile, we also found a class of non-aromatic acid components that can inhibit PD-L1 in blood activating and stasis resolving Chinese medicine. Combining with the theory of inter-species synergistic evolution, we propose that the synergy between COX-2 and PD-L1 in the immune escape of circulating tumor cells may be an important mechanistic link for the inhibitory effect of blood activating and stasis resolving Chinese medicine on metastasis, which have multi-component multi-target. In order to test our hypothesis, our group built a virtual, dynamic and sensitive computational biological model to mimic tumor blood metastasis in vivo, and established MC38-hPDL1 gene modified cell lines and the human PD-1 expressing mouse model with C57BL/6 background. By employing quantitative pharmacological methods, and using models from molecules to cells to animals, we aim to explore the integrated synergy mechanism of multi-component multi-target inhibition of metastasis by blood activating and stasis resolving method/Chinese medicine from a holistic perspective, and to provide some strategies for the study of cancer treatment principles and method.