Background: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 ant...Background: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.Methods: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.Results: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.Conclusion:L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.展开更多
基金National Natural Science Foundation of China(Nos.81720108006,81974062)。
文摘Background: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.Methods: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.Results: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.Conclusion:L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.
