Antitumor activity of anlotinib in malignant melanoma: modulation of angiogenesis and vasculogenic mimicry

Arch Dermatol Res. 2024 Jul 3;316(7):447. doi: 10.1007/s00403-024-03020-1.

Abstract

Malignant melanoma presents a formidable challenge due to its aggressive metastatic behavior and limited response to current treatments. To address this, our study delves into the impact of anlotinib on angiogenesis and vasculogenic mimicry using malignant melanoma cells and human umbilical vein endothelial cells. Evaluating tubular structure formation, cell proliferation, migration, invasion, and key signaling molecules in angiogenesis, we demonstrated that anlotinib exerts a dose-dependent inhibition on tubular structures and effectively suppresses cell growth and invasion in both cell types. Furthermore, in a mouse xenograft model, anlotinib treatment resulted in reduced tumor growth and vascular density. Notably, the downregulation of VEGFR-2, FGFR-1, PDGFR-β, and PI3K underscored the multitargeted antitumor activity of anlotinib. Our findings emphasize the therapeutic potential of anlotinib in targeting angiogenesis and vasculogenic mimicry, contributing to the development of novel strategies for combating malignant melanoma.

Keywords: Angiogenesis; Anlotinib; Malignant melanoma; Multitargeted therapy; Therapeutic innovation; Vasculogenic mimicry.

MeSH terms

  • Angiogenesis
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Human Umbilical Vein Endothelial Cells*
  • Humans
  • Indoles* / pharmacology
  • Indoles* / therapeutic use
  • Melanoma* / drug therapy
  • Melanoma* / pathology
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic* / drug therapy
  • Neovascularization, Pathologic* / pathology
  • Quinolines* / administration & dosage
  • Quinolines* / pharmacology
  • Quinolines* / therapeutic use
  • Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology
  • Vascular Endothelial Growth Factor Receptor-2* / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2* / metabolism
  • Xenograft Model Antitumor Assays*

Substances

  • Quinolines
  • anlotinib
  • Indoles
  • Vascular Endothelial Growth Factor Receptor-2
  • Receptor, Fibroblast Growth Factor, Type 1
  • Antineoplastic Agents
  • FGFR1 protein, human
  • Angiogenesis Inhibitors
  • Receptor, Platelet-Derived Growth Factor beta
  • KDR protein, human