Huang Jiawei, Qiu Mengyuan, Wan Li, Wang Gui, Huang Tongzhou, Chen Zhixin, Jiang Songmin, Li Xiaokun, Xie Lixiao, Cai Lin
Department of Biopharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Cell Physiol Biochem. 2018;45(4):1690-1699. doi: 10.1159/000487737. Epub 2018 Feb 22.
BACKGROUND/AIMS: TGF-β1 is beneficial during early liver disease but is tumor-progressive during late stages especially for hepatocellular carcinoma (HCC). Thus, exploring the underlying mechanisms may provide information about a potentially therapeutic role of TGF-β1 in HCC.
Western blot and real-time quantitative PCR were used to quantify FGFR4 expression in HCC cell lines and a normal liver cell line. After constructing the best silencing FGFR4 expression vector, migration and invasiveness of TGF-β1 in HCC was studied in vitro and in vivo. Western blot was used to study the mechanism of TGF-β1 induction on FGFR4 expression with various inhibitors.
HepG2 cell lines had the most FGFR4 expression, and data show that silencing FGFR4 suppressed cell proliferation, invasion and migration in HCC induced by TGF-β1 in vitro and in vivo. Moreover, TGF-β1 induced FGFR4 expression through the ERK pathway.
Promoting FGFR4 expression via the ERK pathway, TGF-β1 contributes to HCC invasion and metastasis.
背景/目的：转化生长因子-β1（TGF-β1）在早期肝脏疾病中有益，但在晚期尤其是肝细胞癌（HCC）中具有促肿瘤进展作用。因此，探究其潜在机制可能为TGF-β1在HCC中的潜在治疗作用提供信息。
采用蛋白质免疫印迹法和实时定量聚合酶链反应来定量HCC细胞系和正常肝细胞系中FGFR4的表达。构建最佳的沉默FGFR4表达载体后，在体外和体内研究TGF-β1在HCC中的迁移和侵袭能力。使用蛋白质免疫印迹法，通过各种抑制剂研究TGF-β1诱导FGFR4表达的机制。
HepG2细胞系中FGFR4表达最多，数据表明，沉默FGFR4可在体外和体内抑制TGF-β1诱导的HCC细胞增殖、侵袭和迁移。此外，TGF-β1通过ERK途径诱导FGFR4表达。
TGF-β1通过ERK途径促进FGFR4表达，有助于HCC的侵袭和转移。
