Fbxw7对肝癌边缘群细胞生物学功能的调控及机制研究

肝癌边缘群细胞（Side Population, SP）是一群具有干细胞特性的细胞，它们较主群细胞具有自我更新、致瘤能力强、耐药特性突出、细胞周期静止等特点，在肝癌的转移与侵袭中也起了关键的作用。在我们前期肝癌的研究中发现泛素—蛋白酶体系统中的蛋白Fbxw7能够影响肝癌的增殖、侵袭和转移，而大量文献报道Fbxw7通过调节肿瘤干细胞的细胞周期进而影响肿瘤的发生、发展和转移。本研究拟通过体外增殖、侵袭、迁移实验及动物体内成瘤、转移模型等探索Fbxw7对肝癌 SP 细胞的作用，并通过调节并测定Fbxw7及其标靶基因Cyclin E、c-Myc、Notch等在SP细胞中的表达水平，印证其对SP细胞增殖、侵袭、转移能力的影响。从而阐明Fbxw7在调控肝癌 SP 细胞增殖、侵袭、转移及耐药中的部分作用机制，为研究新的肝癌治疗策略奠定基础。

The side population (SP) cells of liver cancer are a group of cells with stem cell characteristics. They have self-renewal, strong tumorigenic ability, prominent drug resistance, and cell cycle quiescence. They also play a key role in the metastasis and invasion of liver cancer. In our previous studies, it was found that the protein Fbxw7 of the ubiquitin-proteasome system can affect the proliferation, invasion and metastasis of liver cancer. A large number of reports have reported that Fbxw7 affects the occurrence, development and metastasis of tumor cells by regulating the cell cycle of cancer stem cells. In this study, we explored the effects of Fbxw7 on hepatocellular carcinoma SP cells in vitro through proliferation, invasion, migration experiments and tumor formation and metastasis models in animals. We analyzed the expression level in SP cells to confirms its influence on SP cell proliferation, invasion and metastasis via regulating and measuring Fbxw7 and its target genes Cyclin E, c-Myc, Notch, etc. The aim is elucidating the mechanism of Fbxw7 in regulating the proliferation, invasion, metastasis and drug resistance of hepatocellular carcinoma SP cells, and laying a foundation for the study of new liver cancer treatment strategies.