Helicobacter pylori promote gastric cancer cells invasion through a NF-kappaB and COX-2-mediated pathway

World J Gastroenterol. 2005 Jun 7;11(21):3197-203. doi: 10.3748/wjg.v11.i21.3197.


Aim: To examine the effects of Helicobacter pylori (H pylori) infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism.

Methods: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel analysis. The expression of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and beta-galactosidase activities. Lastly, the protein-DNA interaction was confirmed by an electrophoretic mobility shift assay.

Results: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC, a nuclear factor kappaB (NF-kappaB) inhibitor; (2) the induction of MKN-45 cells invasion by H pylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects; (3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-kappaB to this promoter.

Conclusion: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-kappaB and COX-2 mediated pathway, as COX-2 or NF-kappaB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclooxygenase 2
  • Gene Expression Regulation, Neoplastic
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / pathology
  • Helicobacter pylori*
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Membrane Proteins
  • NF-kappa B / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / genetics


  • Membrane Proteins
  • NF-kappa B
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Matrix Metalloproteinase 9