研究发现外泌体对大肠癌侵袭转移起重要作用，但确切机制仍未清楚。我们前期研究发现外泌体膜上的Wnt3a能竞争性的结合大肠癌细胞膜上Fz受体，并与β-catenin/TCF信号的活化和大肠癌侵袭转移呈正相关，中药丹参的有效成分丹参酮IIA能够抑制β-catenin信号通路抗大肠癌转移，因此我们提出“外泌体可能通过细胞膜上Fz受体，激活β-catenin/TCF信号通路促进大肠癌转移”的科学假说。 . 本研究采用质粒转染、RNAi、CHIP等技术，研究外泌体通过Fz受体，激活β-catenin/TCF信号通路促进大肠癌转移的机制；构建主动识别Wnt3a+外泌体的新型中药靶向给药系统丹参酮IIA纳米粒，探讨丹参酮IIA纳米靶向Wnt3a/Fz受体抑制β-catenin/TCF通路抗大肠癌转移的机制。这对于揭示大肠癌转移机制，探索大肠癌的分子靶向治疗具有重要意义。

Evidence suggests that exosomes play an important role in invasion and metastasis of human colorectal cancer (CRC), through yet undefined mechanism. Our preliminary data indicated that wnt3a in the membrane of exosomes competitively interacted with membrane bound Fz receptors of the CRC cells, to activate β-catenin/TCF signaling and promote invasion and metastasis. We hypothesize that exosomes may promote CRC invasion and metastasis via affecting the Fz receptor/β-catenin/TCF signaling axis. . We therefore propose to use plasmid transfection, RNAi and ChIP technologies to mechanistically investigate this action of exosomes. Based on our observation of inhibitory effect of Tanshinone IIA, an effective component of Chinese medicinal herb Salviae Miltiorrhizae, on β-catenin signaling mediated CRC metastasis, we propose to generate novel wnt3a+exosomes-targeting Traditional Chinese Medicine Tanshinone IIA nanoparticles, to explore the action mechanism of their inhibition on wat3a/Fz receptor/β-catenin/TCF signaling mediated CRC metastasis. Our results will elucidate how CRC metastasizes and provide novel options for targeted therapy against this malignancy.