Inhibition of gastric cancer cells associated angiogenesis by 15d-prostaglandin J2 through the downregulation of angiopoietin-1

Cancer Lett. 2006 Nov 18;243(2):246-54. doi: 10.1016/j.canlet.2005.11.039. Epub 2006 Jan 18.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been shown to inhibit angiogenesis. We showed that treatment with 15d-PGJ(2), a PPARgamma ligand, downregulate the expressions of angiopoietin-1 (Ang-1) in gastric cancer cells MKN45. The medium of MKN45 cells treated with 15d-PGJ(2) significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, Matrigel plug assay revealed that 15d-PGJ(2) reduced in vivo angiogenesis induced by MKN45 cells. These modulations were restored by the addition of recombinant Ang-1. Our findings supported that 15d-PGJ(2) suppressed angiogenesis of gastric cancer cells by downregulation of Ang-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiopoietin-1 / genetics*
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Female
  • Gene Expression Profiling
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Neovascularization, Physiologic / drug effects
  • Oligonucleotide Array Sequence Analysis
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • 15-deoxyprostaglandin J2
  • Angiogenesis Inhibitors
  • Angiopoietin-1
  • Vascular Endothelial Growth Factor A
  • Prostaglandin D2