基于炎症促进肿瘤发生发展的具体机制开发抗肿瘤新药，是当前极具潜力的癌症治疗策略之一。最近相关研究表明，SphK1/S1P/YAP通路在炎症促进肿瘤发生发展中发挥重要作用，靶向该通路将成为有效治疗炎症相关性癌症的新策略。黄芩苷具有显著的抗炎和抗肿瘤活性，但是黄芩苷对炎症相关性癌症的抑制作用及其机制，尚不明确，有待阐明。前期研究利用多种培养体系模拟肿瘤炎症微环境，发现黄芩苷可能通过调控SphK1/S1P/YAP通路发挥抗肿瘤作用。据此，本项目通过体外构建多种培养体系，体内建立多种小鼠炎症相关性癌症模型，研究黄芩苷对炎症相关性癌症发生发展的抑制作用，并以SphK1/S1P/YAP通路为切入点，阐明其作用机制，同时探索Src在SphK1/S1P诱导YAP活化中的桥梁作用。本项目为黄芩苷的抗肿瘤研究提供理论依据，并为抗肿瘤药物研发提供新的思路。

Currently, it is one of most potential strategies for cancer therapy to target the mechanism by which inflammation promotes cancer initiation and progression. Recent studies have reported that SphK1/S1P/YAP pathway plays an important role in the cancer initiation and progression driven by inflammation. Targeting SphK1/S1P/YAP pathway may be a new therapeutic strategy for inflammation-associated cancer. Baicalin exerts dramatic anti-inflammatory and anticancer activities. However, it still remains to be elucidated the potential mechanism of the inhibitory effects of baicalin on the initiation and progression in inflammation-associated cancer. Our previous study demonstrated that baicalin might exert anticancer effect on cancer cells in various culture system in vitro via SphK1/S1P/YAP pathway. This project aims to investigate the inhibitory effects of baicalin on the cancer initiation and progression of inflammation-associated cancer by establishing various culture system in vitro and building many kinds of inflammation-associated cancer in mice in vivo. Moreover, SphK1/S1P/YAP pathway is regarded as the breakthrough point, and we further explore the bridge role of Src in YAP activation induced by SphK1/S1P, to fully illustrate the anticancer mechanism of baicalin in the inflammatory microenvironment. In conclusion, this project provides theoretical basis for the anticancer mechanism research of baicalin, and gives new insight to the development of promising anticancer therapeutic agents.