title: Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma.
abstract: Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae, is a sulfated polysaccharide and, as a novel marine biological material, has been used to treat various disorders in China, Korea, Japan and other countries. In the present study, we demonstrated that fucoidan derived from Undaria pinnatifida sporophylls significantly inhibits the hypoxia-induced expression, nuclear translocation and activity of HIF-1α, the synthesis and secretion of VEGF-C and HGF, cell invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line. Fucoidan also suppressed lymphangiogenesis in vitro and in vivo. In addition, accompanied by a reduction in the HIF-1α nuclear translocation and activity, fucoidan significantly reduced the levels of p-PI3K, p-Akt, p-mTOR, p-ERK, NF-κB, MMP-2 and MMP-9, but increased TIMP-1 levels. These results indicate strongly that the anti-metastasis and anti-lymphangiogenesis activities of fucoidan are mediated by suppressing HIF-1α/VEGF-C, which attenuates the PI3K/Akt/mTOR signaling pathways.
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. thm0529@126.com.
authors.forename: Hongming
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. yangyazong123.@126.com.
authors.forename: Yazong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. weihengyun@126.com.
authors.forename: Hengyun
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. harryblood1989@126.com.
authors.forename: Zundong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. caredliu@126.com.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. m981765863@icloud.com.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. 18641548759@163.com.
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: College of Life Sciences, Liaoning Normal University, Dalian 116081, China. houlin@lnnu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. zouxiangyang@126.com.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D042583:Lymphangiogenesis / Q000187:drug effects; D008207:Lymphatic Metastasis / Q000517:prevention & control; D008297:Male; D051379:Mice; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D044648:Undaria / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011134:Polysaccharides; C007789:fucoidan
keywords: HIF-1α; fucoidan; hypoxia; lymphangiogenesis; metastasis