Genistein为天然异黄酮类物质，可以抑制酪氨酸激酶活性，具有较强的抗肿瘤作用和较低的毒副作用。我们在前期研究中发现，genistein可以在体内外抑制结肠癌细胞的侵袭转移。对其下游转移相关基因进行筛选，发现FLT4和MMP2在genistein处理后表达水平降低，同时Akt、p38 MAPK及ERK1/2的磷酸化水平受到抑制。FLT4 为血管内皮生长因子受体，有报道指出其活化可以激活p38 MAPK通路，而MAPK也被报道可以促进FLT4及MMP2表达。因此我们推断genistein通过抑制蛋白激酶磷酸化抑制FLT4和MMP2表达，进而抑制结肠癌细胞侵袭转移，且FLT4可通过p38 MAPK通路调控MMP2表达和结肠癌细胞侵袭转移。本项目拟通过体内外实验阐明genistein通过蛋白激酶、FLT4及MMP2通路抑制结肠癌转移的机制，为该小分子化合物的临床应用奠定理论基础。

Genistein belongs to natural isoflavones, which can inhibit the tyrosine kinase activity, and has strong anti-tumor effect and lower toxicity. In the previous study, we found that genistein could inhibit the invasion and metastasis of colon cancer cells in vivo, and its downstream metastasis-associated genes were screened and it was found that FLT4 and MMP2 expression levels were decreased after genistein treatment while Akt, p38 MAPK and ERK1/2 were inhibited at the phosphorylation level. FLT4 is a vascular endothelial growth factor receptor, and it has been reported that its activation could promote p38 MAPK pathway, and MAPK has also been reported to promote FLT4 and MMP2 expression. Therefore, we hypothesize that genistein could inhibit FLT4 and MMP2 expression through inhibition of protein kinase phosphorylation, thereby inhibiting colon cancer cell metastasis, and FLT4 could regulate MMP2 and metastasis by p38 MAPK pathway. The project intends to illustrate the mechanism of genistein inhibition of colon cancer metastasis by the network composed of protein kinase, FLT4 and MMP2, and lay the theoretical foundation for the clinical application of this small molecule compounds.