结直肠癌是常见的消化道肿瘤，其转移是导致死亡的主要原因。化疗是防治转移的主要手段，但是其治愈率有限，且副作用明显。Genistein为异黄酮类物质，具有较强的肿瘤转移抑制作用，但其类雌激素作用限制了其应用。我们的前期工作对genistein进行改构获得了一个新的小分子化合物，初步体外实验证实该小分子可以有效抑制多种结直肠癌细胞的迁移及侵袭能力，而无明显类雌激素作用;磷酸化抗体筛选提示改构的小分子相对于genistein具有更特异的磷酸化通路抑制谱。为进一步验证该小分子在体内的抗转移疗效并探讨其作用的确切分子机制，本研究拟采用裸鼠结肠癌原位种植模型明确该小分子对结直肠癌的体内转移抑制作用，并基于磷酸化底物分析获取的可能蛋白激酶靶点，定制qPCR芯片获得候选靶点相关的关键分子，再经体内外干预实验进行验证，明确其抗转移机制，为该小分子化合物的临床应用奠定理论基础。

Colorectal cancer is common in gastrointestinal tumors, and its metastasis is the leading cause of death. Chemotherapy is the primary means of preventing metastasis with limited cure rate and obvious side effects. Genistein belongs to isoflavones and is potent in inhibiting tumor metastasis, but its estrogen-like effects limit its application. In our previous work, we changed the configuration of genistein and acquired a new small molecule compound. Preliminary in vitro experiments confirmed that the small molecule could effectively suppress migration and invasion abilities of multiple colorectal cancer cells, without significant estrogen-like effects. Phosphorylation antibody screening indicated that the small molecule had a more specific spectrum in inhibiting phosphorylation pathways. To further verify the anti-metastasis efficacy of the small molecule in vivo and explore the exact molecular mechanisms, this study intends to adopt nude mice orthotopic implantation model to clarify the role of the small molecule in inhibiting colorectal cancer metastasis. Further, we will adopt customized qPCR array based on potential protein kinase targets candidates acquired from phosphorylation substrate analysis to obtain relevant key molecules, and validate the potential targets by in vitro and in vivo intervention experiments. In this way, we would clear the anti-metastasis mechanisms of the small molecule and lay the foundation for its clinical application.