Artesunate inhibits vasculogenic mimicry in choroidal melanoma through HIF-1 α/ VEGF/PDGF pathway

Acta Histochem. 2024 Oct;126(5-7):152174. doi: 10.1016/j.acthis.2024.152174. Epub 2024 Jul 7.

Abstract

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

Keywords: Artesunate; Choroidal melanoma; Vasculogenic mimicry.

MeSH terms

  • Artesunate* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Choroid Neoplasms* / drug therapy
  • Choroid Neoplasms* / metabolism
  • Choroid Neoplasms* / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Neovascularization, Pathologic* / drug therapy
  • Neovascularization, Pathologic* / metabolism
  • Neovascularization, Pathologic* / pathology
  • Platelet-Derived Growth Factor* / metabolism
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor A
  • Artesunate
  • HIF1A protein, human
  • VEGFA protein, human