纳米金粒子通过TGF-β信号通路抑制结肠癌肝转移的机制研究

肝转移是结肠癌的主要死亡原因之一，TGF-β信号通路在结肠癌发生发展中具有重要作用。纳米金粒子(AuNPs)的应用是现代肿瘤研究的突破点。然而,AuNPs对结肠癌生长和转移的作用及其分子生物学机制尚不清楚。申请者的前期研究发现，AuNPs可降低结肠癌细胞中TGF-β分泌及下游信号表达，抑制结肠癌细胞增殖与迁移；同时，AuNPs抑制TGF-β诱导的结肠癌体内生物成像动物模型中的TGF-β信号通路,并抑制肿瘤的生长。本课题拟利用结肠癌细胞系、人结肠癌肝转移瘤原代细胞培养、结肠癌原位种植及肝转移模型，探讨AuNPs对结肠癌肝转移的作用，并通过干扰TGF-β通路主要调控基因Smad4研究其分子生物学机制，为结肠癌肝转移的治疗提供新思路和理论依据。

Liver metastasis is one of the leading causes of death in colon cancer. TGF-β signaling pathway plays an important role in the development and progression of colon cancer. The application of gold nanoparticles (AuNPs) to the management of cancer is currently the new breakthrough in cancer research. However, the role of AuNPs on tumor growth and metastasis in colon cancer and the mechanism by which AuNPs regulate tumor growth and liver metastasis in colon cancer are unclear. Our preliminary in vitro experiment provided evidences that AuNPs inhibit tumor proliferation and migration, and significantly reduce the secretion of TGF-β and inhibit the expression of downstream signaling factors. In addition, we proved that AuNPs inhibit tumor growth and down-regulate TGF-β signaling of colon cancer in vivo, through a TGF-β inducible bioluminescence animal model. The objective of this project is to elucidate the role of AuNPs in colon cancer growth and liver metastasis, through three colon cancer cell lines, isolating and culturing human cancer cells derived form colon cancer liver metastasis, and orthotopic colon cancer and liver metastasis animal models. Smad4, an important transduction factor of the TGF-β signaling pathway, will be overexpressed or knockdown to explore the molecular mechanism by which AuNPs regulate colon cancer liver metastasis. This study will provide new idea and theoretical evidence for the treatment of colon cancer liver metastasis.