L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression

• Published in: Chinese medical journal 2022-12, Vol.135 (24), p.2956-2967
• Main Authors: Zhu, Biqiang, Zheng, Jingjing, Hong, Gaichao, Bai, Tao, Qian, Wei, Liu, Jinsong, Hou, Xiaohua
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antibodies; Apoptosis; Bile Duct Neoplasms - metabolism; Bile Ducts, Intrahepatic - metabolism; Bile Ducts, Intrahepatic - pathology; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cholangiocarcinoma; Cholangiocarcinoma - drug therapy; Cholangiocarcinoma - metabolism; Cyclin-dependent kinases; Disease Models, Animal; Endothelial Cells - metabolism; Fucose - pharmacology; Fucose - therapeutic use; Gene Expression Regulation, Neoplastic; Humans; Investigations; Kinases; Laboratory animals; Metastasis; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy; Mitogen-Activated Protein Kinase 7 - metabolism; Original; Proteins; Software; STAT3 Transcription Factor - metabolism; Statistical significance; Ultrasonic imaging; Variance analysis
• ISSN: 0366-6999; 2542-5641; 2542-5641
• DOI: 10.1097/CM9.0000000000002368

Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on the progression of CCA has not been well investigated. This study aimed to determine whether L-fucose induced the inhibition of CCA and its possible mechanism. The anti-growth activity was determined using Cell Counting Kit-8 assay, colony formation assays, Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, and cell cycle analysis. The anti-metastasis activity was determined by wound healing, transwell, and invasion assays. The anti-angiogenesis activity was determined by tube formation and transwell assays. MicroRNAs that may be involved in the L-fucose-induced CCA inhibition was analyzed using bioinformatics methods. The preclinical therapeutic efficacy was mainly estimated by ultrasound in xenograft nude mouse models. Differences were analyzed via Student's t test or one-way analysis of variance. L-Fucose induced apoptosis and G0/G1 cell cycle arrest, inhibited cell epithelial-mesenchymal transition of CCA cells, and additionally inhibited tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, leading to a decrease in cell proliferation, metastasis, and angiogenesis. Mechanistically, L-fucose induced microRNA-200b (miR-200b) upregulation, and mitogen-activated protein kinase 7 (MAPK7) downregulation was found to be targeted by miR-200b, with decreased cell proliferation and metastasis. Additionally, phosphorylated signal transducer and activator of transcription 3 was found to be downregulated after L-fucose treatment. Finally, in vivo experiments in CCA xenograft models also confirmed the antitumor properties of L-fucose. L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.