A novel angiogenesis inhibitor, Ki23057, is useful for preventing the progression of colon cancer and the spreading of cancer cells to the liver

Eur J Cancer. 2007 Nov;43(17):2612-20. doi: 10.1016/j.ejca.2007.09.002. Epub 2007 Oct 18.

Abstract

Ki23057 is a new, small synthetic tyrosine kinase inhibitor that blocks autophosphorylation of the VEGF receptor2 (VEGFR2). To determine the effect of Ki23057 as an anti-angiogenic agent, we studied the effect of Ki23057 for colon cancer and vascular endothelial cells in vitro and in vivo. Ki23057 inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs), whereas no inhibitory effect of Ki23057 on the proliferation of three colon cancer cells (LM-H3, LoVo and LS174T) was observed by means of the cell count assay. Ki23057 inhibited tube formation of HUVECs. Immunoprecipitation demonstrated that Ki23057 inhibited tyrosine phosphorylation of VEGFR2 in HUVECs. Ki23057 exhibited a significant inhibitory effect on the growth of the xenografted LM-H3 tumours and the spreading of cancer cells to the liver. Anti-CD31 antibody stained significantly fewer microvessels in the xenografted tumours treated with Ki23057 compared with controls. Ki23057 may be a promising new antiangiogenic agent for colon cancer.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Cell Division
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms*
  • Endothelial Cells
  • Humans
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / secondary
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Phosphorylation
  • Quinolines / therapeutic use*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Ki23057
  • Quinolines
  • Vascular Endothelial Growth Factor A