肿瘤转移是恶性肿瘤治疗的核心问题，而肿瘤微环境作为其驱动因素，它的调节是抑制肿瘤转移的关键。目前认为，细胞代谢可整体调控肿瘤微环境；同时顺铂、索拉非尼有通过改变微环境促转移的报道。我们的前期试验表明，中药重楼的活性成分重楼皂苷（RPS）具有多成分、多靶点性，可显著抑制转移性肺癌；预实验也显示RPS与铂类药联用有增效减毒的优势。为进一步证明“RPS可作用于‘肿瘤微环境-细胞代谢-信号通路’的信号轴，进而与顺铂、索拉非尼联用，可增效减毒发挥抗转移作用”的假说，本项目拟从转移性肺癌模型的建立、活性评价、药效物质基础研究到基于肿瘤微环境的机制探讨，全面分析RPS发挥抗转移作用的药效物质基础及作用机制；同时对比顺铂、索拉非尼等抗癌药，分析RPS与其联用的优势。总之，本项目的顺利实施将促进RPS的临床应用，丰富中药基于肿瘤微环境干预发挥抗转移作用的基础理论，同时为顺铂、索拉非尼的合理用药奠定理论依据。

Tumor metastasis is an important clinical issue for the malignant tumor treatment. Meanwhile, tumor microenvironment as the driving factor for the tumor metastasis, its intervention is pivotal to inhibiting the tumor metastasis. As we know, cell metabolism influences tumor microenvironment. At the same time, cisplatin and sorafenib promote tumor metastasis through the regulation of the tumor microenvironment. Rhizoma Paridis is regarded as a common herb and one of the main materials used in the anticancer Traditional Chinese medicine (TCM) prescription. Rhizoma Paridis Saponins (RPS) as its effective part shows multi-component, multi-target and strong inhibition of the pulmonary metastasis. Our preliminary experiments also indicated that combination of RPS and platinum enhanced efficacy and reduced toxicity of platinum. In order to prove the hypothesis that “RPS can act on the axis ‘tumor microenvironment-cell metabolism-signaling pathway’, and further enhance efficacy and reducing toxicity of cisplatin and sorafenib to inhibit the pulmonary metastasis”, we are going to set up 3 kinds of metastatic lung cancer models, evaluate the activity of RPS used alone or combined with chemotherapy, explore its material basis and analyze the mechanisms of its anti-metastatic lung cancer effects base on the tumor microenvironment intervention. All in all, this project will promote the clinical application of RPS, and enrich the pharmacological theory of TCM based on the targets on the tumor microenvironment to inhibit the metastatic lung cancer. Furthermore, it may serve as an indication for the safe medication and rational administration of the anticancer drugs such as cisplatin and sorafenib.