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Oncotarget. 2016 Jun 21;7(25):38025-38035. doi: 10.18632/oncotarget.9443.

Fucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells.

Author information

1
Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.
2
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China.

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.

KEYWORDS:

PROX1; fucoidan; lymphangiogenesis; lymphatic endothelial cells; lymphatic metastasis

PMID:
27203545
PMCID:
PMC5122369
DOI:
10.18632/oncotarget.9443
[Indexed for MEDLINE]
Free PMC Article

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