Open AccessFucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells
Author(s) -
Yazong Yang,
Zixiang Gao,
Yue Ma,
Hongming Teng,
Zundong Liu,
Hengyun Wei,
Yiming Lu,
Xiaofang Cheng,
Hui Lin,
Xiangyang Zou
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.9443
Subject(s) - fucoidan , lymphangiogenesis , lymphatic endothelium , cancer research , lymphatic system , pi3k/akt/mtor pathway , vascular endothelial growth factor c , medicine , metastasis , microbiology and biotechnology , biology , immunology , vascular endothelial growth factor , signal transduction , cancer , vascular endothelial growth factor a , biochemistry , polysaccharide , vegf receptors
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.