Effects of thalidomide on parameters involved in angiogenesis: an in vitro study

J Neurooncol. 2003 Sep;64(3):193-201. doi: 10.1023/a:1025618022921.

Abstract

In an attempt to elucidate the mechanism(s) of action of thalidomide, a reportedly antiangiogenic molecule recently tested in the treatment of relapsing malignant gliomas, we performed an in vitro study on the following parameters: (a) effect of thalidomide on proliferation of endothelial cells; (b) effect of thalidomide on expression of alpha(v)beta3 integrin on the surface of endothelial cells; (c) effect of thalidomide on the release by endothelial cells of MMP-2, IL-8 and TNF-alpha. The results show that thalidomide inhibits endotelial cell proliferation induced by bFGF and VEGF, more so if the cells are grown on vitronectin; moreover, treatment with thalidomide reduces the release of MMP-2 and IL-8 by endothelial cells, suggesting a further pathway for the antiangiogenic activity of drug. On the other hand, thalidomide does not modify expression of alpha(v)beta3 on endothelial cells.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Endothelial Growth Factors / physiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / growth & development
  • Endothelium, Vascular / metabolism
  • Fibroblast Growth Factor 2 / physiology
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Intercellular Signaling Peptides and Proteins / physiology
  • Interleukin-8 / metabolism
  • Lymphokines / physiology
  • Matrix Metalloproteinase 2 / metabolism
  • Neovascularization, Pathologic / prevention & control
  • Neovascularization, Physiologic / drug effects*
  • Receptors, Cell Surface / metabolism
  • Thalidomide / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vitronectin / physiology

Substances

  • Angiogenesis Inhibitors
  • Endothelial Growth Factors
  • Integrin alphaVbeta3
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Lymphokines
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vitronectin
  • Fibroblast Growth Factor 2
  • Thalidomide
  • Matrix Metalloproteinase 2