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.
Highlights
Melanoma is one of the most malignant and aggressive types of cancer worldwide, and the identification of new targets for treating melanoma is urgently needed
propylene glycol alginate sodium sulfate (PSS) was investigated by surface plasmon resonance (SPR) analysis for its affinity with fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor 165 (VEGF165)
FGF2 is a proangiogenic factor involved in tumor angiogenesis, invasion melanoma B16-F10 cells
Summary
Melanoma is one of the most malignant and aggressive types of cancer worldwide, and the identification of new targets for treating melanoma is urgently needed. Melanoma cells have been reported to constitutively express fibroblast growth factor 2 (FGF2) [1,2], which is an autocrine factor and promotes the proliferation, angiogenesis, and metastasis of melanoma cells. FGF2 is commonly considered one of the potential targets for treating melanoma, and may be used with other targets to synergistically enhance therapeutic efficacy [3]. Mar. Drugs 2019, 17, 257; doi:10.3390/md17050257 www.mdpi.com/journal/marinedrugs.
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