Celecoxib inhibits Helicobacter pylori-induced invasion of gastric cancer cells through an adenine nucleotide translocator-dependent mechanism

Anticancer Agents Med Chem. 2013 Oct;13(8):1267-72. doi: 10.2174/18715206113139990324.

Abstract

Cyclooxygenase-2 (COX-2) inhibitor, celecoxib, causes growth inhibition of human gastric carcinoma cells, but it remains unclear whether celecoxib inhibits Helicobacter pylori-induced invasion of gastric cancer cells. The adenine nucleotide translocator (ANT) is a mitochondrial bi-functional protein. We speculate that ANT-dependent pathways might contribute to H. pylori-induced invasion and metastasis of gastric cancer cells. Therefore, in the present study, we evaluate the effect of celecoxib on H. pylori-induced gastric cancer cell motility and invasion. We also explore the role of ANTs in H. pylori-induced gastric cancer cell motility and invasion of gastric cancer cell line AGS. Our results demonstrate that celecoxib induces anoikis-like apoptosis and suppresses the proliferation and invasion of gastric cancer cells induced by H. pylori in culture. RT-PCR and Western blot analysis indicates that celecoxib upregulates the expression of ANT1 and ANT3; however, celecoxib did not increase the expression of ANT2. Our results suggest that celecoxib could be an effective means for suppressing proliferation and invasion of gastric cancer cells induced by H. pylori through an adenine nucleotide translocator-dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anoikis / drug effects
  • Celecoxib
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Helicobacter Infections / complications
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / physiology*
  • Humans
  • Mitochondrial ADP, ATP Translocases / metabolism*
  • Neoplasm Invasiveness
  • Protein Isoforms / metabolism
  • Pyrazoles / pharmacology*
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Sulfonamides / pharmacology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Protein Isoforms
  • Pyrazoles
  • Sulfonamides
  • Mitochondrial ADP, ATP Translocases
  • Celecoxib