The Inhibitory Effect of Propylene Glycol Alginate Sodium Sulfate on Fibroblast Growth Factor 2-Mediated Angiogenesis and Invasion in Murine Melanoma B16-F10 Cells In Vitro

Mar Drugs. 2019 Apr 29;17(5):257. doi: 10.3390/md17050257.

Abstract

Melanoma is one of the most malignant and aggressive types of cancer worldwide. Fibroblast growth factor 2 (FGF2) is one of the critical regulators of melanoma angiogenesis and metastasis; thus, it might be an effective anti-cancer strategy to explore FGF2-targeting drug candidates from existing drugs. In this study, we evaluate the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) on FGF2-mediated angiogenesis and invasion. The data shows that FGF2 selectively bound to PSS with high affinity. PSS inhibited FGF2-mediated angiogenesis in a rat aortic ring model and suppressed FGF2-mediated invasion, but not the migration of murine melanoma B16-F10 cells. The further mechanism study indicates that PSS decreased the expression of activated matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and also suppressed their activity. In addition, PSS was found to decrease the level of Vimentin in B16-F10 cells, which is known to participate in the epithelial-mesenchymal transition. Notably, PSS did not elicit any changes in cancer cell viability. Based on the results above, we conclude that PSS might be a potential drug to regulate the tumor microenvironment in order to facilitate the recovery of melanoma patients.

Keywords: FGF2; MMP-2; MMP-9; angiogenesis; invasion; propylene glycol alginate sodium sulfate.

MeSH terms

  • Alginates / pharmacology*
  • Alginates / therapeutic use
  • Animals
  • Aorta / drug effects
  • Aquatic Organisms / chemistry
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane
  • Drug Evaluation, Preclinical
  • Epithelial-Mesenchymal Transition
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Laminaria / chemistry
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Physiologic / drug effects
  • Organ Culture Techniques
  • Rats
  • Skin Neoplasms / blood supply
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Tumor Microenvironment / drug effects

Substances

  • Alginates
  • propylene glycol alginate sodium sulfate
  • Fibroblast Growth Factor 2