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World J Gastroenterol. 2005 Jun 7;11(21):3197-203.

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

Author information

1
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan, China.

Abstract

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.

PMID:
15929167
PMCID:
PMC4316048
DOI:
10.3748/wjg.v11.i21.3197
[Indexed for MEDLINE]
Free PMC Article

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