Chen Yi-Hui, Yang Shao-Hua, Liu Li-Xin, Hu Sheng, Wang Xue-Jun, Liao Zhou-Jun, Huan Yun-Feng, He Kai, Zhang Xiao-Wen
The Second Affiliated Hospital of Kunming Medical University, Department of Hepatobiliary Surgery, Kunming, Yunnan, China.
The Second Affiliated Hospital of Kunming Medical University, Department of Hepatobiliary Surgery, Kunming, Yunnan, China.
Dig Liver Dis. 2023 Mar;55(3):400-406. doi: 10.1016/j.dld.2022.07.017. Epub 2022 Aug 20.
The FGF/FGFR signaling axis deregulation of the fibroblast growth factor receptor (FGFR) family is closely related to tumorigenesis, tumor progression and drug resistance to anticancer therapy. And fibroblast growth factor receptor 3 (FGFR3) is one member of this family. In this study, we aimed to investigate the effect of siRNA-induced knockdown of FGFR3 on the biological behaviors of intrahepatic cholangiocarcinoma (ICC). The expression levels of FGFR3 were determined in three intrahepatic cholangiocarcinoma cell lines RBE, HUCCT1 and HCCC9810 cell lines by Western blot. FGFR3 expression in RBE cell line was knocked down by siRNA. Our study found that knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells using Wound healing assay, Transwell migration and invasion assays and Cell proliferation assay. And significantly down-regulated the protein expression levels of MMP2, cyclinD1, and NCadherin, but had no significant effect on MMP9, cyclinD3, vimentin, E-cadherin protein. In addition, we found that ERK/c-Myc presumably is its signaling pathway by bioinformatics analysis and Western blot verification. To sum up, knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells. It demonstrated that FGFR3 probably becomes a therapeutic target for ICC and increases the proportion of potentially curable intrahepatic cholangiocarcinoma patients treated with FGFR inhibitors.
成纤维细胞生长因子受体（FGFR）家族的FGF/FGFR信号轴失调与肿瘤发生、肿瘤进展及抗癌治疗耐药性密切相关。成纤维细胞生长因子受体3（FGFR3）是该家族的一员。在本研究中，我们旨在探讨siRNA诱导的FGFR3基因敲低对肝内胆管癌（ICC）生物学行为的影响。通过蛋白质免疫印迹法检测了三种肝内胆管癌细胞系RBE、HUCCT1和HCCC9810中FGFR3的表达水平。利用siRNA敲低RBE细胞系中的FGFR3表达。我们的研究发现，采用伤口愈合实验、Transwell迁移和侵袭实验以及细胞增殖实验，FGFR3基因敲低抑制了ICC细胞的迁移、侵袭和增殖。并且显著下调了MMP2、细胞周期蛋白D1和N-钙黏蛋白的蛋白表达水平，但对MMP9、细胞周期蛋白D3、波形蛋白、E-钙黏蛋白的蛋白表达无显著影响。此外，通过生物信息学分析和蛋白质免疫印迹验证，我们发现ERK/c-Myc可能是其信号通路。综上所述，FGFR3基因敲低抑制了ICC细胞的迁移、侵袭和增殖。这表明FGFR3可能成为ICC的治疗靶点，并增加接受FGFR抑制剂治疗的潜在可治愈肝内胆管癌患者的比例。
