Celecoxib could reverse the hypoxia-induced Angiopoietin-2 upregulation in gastric cancer

Cancer Lett. 2006 Oct 8;242(1):20-7. doi: 10.1016/j.canlet.2005.10.030. Epub 2005 Dec 9.

Abstract

We investigated the potential effect of Cyclooxygenase-2 (Cox-2) on hypoxia-induced Angiopoietin-2 (Ang-2) expression in gastric cancer cells. Our results revealed that hypoxia augmented Cox-2 and Ang-2 expressions. Also, the hypoxia-induced Ang-2 could be mimicked by CoCl(2) treatment while genestein treatment could partially counteract the hypoxia-induced Ang-2 expression. Celecoxib but not Cox-1 inhibitor sc-560 reversed the hypoxia-induced Ang-2 expression, while this effect could be partially restored by addition of exogenous PGE2. Our findings suggest that the hypoxia-elevated Ang-2 expression in gastric cancer cells may be mediated by both Cox-2-derived PGE2 and HIF-1alpha pathways, while celecoxib could counteract the hypoxia-induced Ang-2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / biosynthesis*
  • Angiopoietins / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Celecoxib
  • Cell Line, Tumor
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dinoprostone / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Pyrazoles / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism*
  • Sulfonamides / pharmacology*
  • Up-Regulation*

Substances

  • Angiopoietin-2
  • Angiopoietins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Celecoxib
  • Dinoprostone