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

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


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.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Homeodomain Proteins / biosynthesis*
  • Humans
  • Lymphangiogenesis / drug effects*
  • Lymphatic Metastasis
  • Male
  • Mice
  • Polysaccharides / administration & dosage
  • Polysaccharides / pharmacology*
  • Random Allocation
  • Signal Transduction / drug effects
  • Tumor Suppressor Proteins / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-3 / biosynthesis*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Homeodomain Proteins
  • Polysaccharides
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein
  • fucoidan
  • FLT4 protein, human
  • Vascular Endothelial Growth Factor Receptor-3