Inhibition of K562 leukemia angiogenesis and growth by selective Na+/H+ exchanger inhibitor cariporide through down-regulation of pro-angiogenesis factor VEGF

Leuk Res. 2011 Nov;35(11):1506-11. doi: 10.1016/j.leukres.2011.07.001. Epub 2011 Jul 23.

Abstract

To investigate the effect of inhibition of Na(+)/H(+) exchanger isoform1 (NHE1) on K562 leukemia-driven angiogenesis, the selective NHE1 inhibitor cariporide was used. Cariporide treatment of K562 resulted in a decrease in pHi and down-regulation of VEGF secretion. The proliferation, migration and in vitro tube formation of human umbilical vein endothelial cells was decreased in cariporide treated K562 condition medium (CM) while VEGF supplement could partially restore the inhibitory effect. Subcutaneous injection of nude mice with cariporide inhibited K562 tumor growth with a reduction of the density of microvessels compared to the control group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / therapeutic use*
  • Blotting, Western
  • Cell Movement
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Guanidines / therapeutic use*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Leukemia / pathology*
  • Leukemia / prevention & control*
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy*
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors*
  • Sulfones / therapeutic use*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Anti-Arrhythmia Agents
  • Guanidines
  • Sodium-Hydrogen Exchangers
  • Sulfones
  • Vascular Endothelial Growth Factor A
  • cariporide