title: Fucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells.
abstract: Lymphangiogenesis is one of the promoters of tumor lymphatic metastasis. Fucoidan which is a fucose-enriched sulfated polysaccharide has effect on various pharmacological activities including anti-metastasis activity. However, the inhibitory effect of fucoidan on lymphangiogenesis remains unclear. Here, fucoidan extracted from U. pinnatifida sporophylls suppressed HLECs proliferation, migration and tube-like structure formation, and had inhibitory effect of tumor-induced lymphangiogenesis in vitro. Additionally, we found that fucoidan had a dose-dependent depressive effect on the expressions of PROX1, vascular endothelial growth factor receptor 3 (VEGFR3), NF-κB, phospho-PI3K and phospho-Akt in HLECs. Moreover, anti-lymphangiogenesis effect of fucoidan was assessed by using mouse tumor model. In summary, fucoidan inhibit tumor lymphangiogenesis and lymphatic metastasis by suppressing the NF-κB/PI3K/Akt signaling pathway through reduced levels of PROX1 and VEGFR3.
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Yazong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Zundong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Hengyun
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: College of Life Sciences, Liaoning Normal University, Dalian, 116081, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D011134:Polysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; D011134:Polysaccharides; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C007789:fucoidan; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: PROX1; fucoidan; lymphangiogenesis; lymphatic endothelial cells; lymphatic metastasis