Gut Liver.  2013 Sep;7(5):552-559.

The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells

• Kim J
• Kim N
• Park JH
• Chang H
• Kim JY
• Lee DH
• Kim JM
• Kim JS
• Jung HC

Abstract

BACKGROUND/AIMS
Helicobacter pylori infection induces cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) overexpression, and these factors may engage in cross-talk. The aim of the present study was to evaluate the effect of H. pylori on EGFR signaling pathways and to determine whether celecoxib has an inhibitory effect on this pathway.
METHODS
The AGS cell line was cocultured with H. pylori G27 and the isogenic cagE- mutant. The expression of COX-2, EGFR, heparin binding-epidermal growth factor (HB-EGF), and transforming growth factor-beta (TGF-beta) was measured by real time-polymerase chain reaction (RT-PCR). Next, Western blot analyses of COX-2, EGFR, total Akt, phosphorylated Akt (pAkt), and phosphorylated glycogen synthase kinase-3beta (pGSK3beta) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 micromol/L).
RESULTS
H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-beta, as detected by RT-PCR. However, AGS cells treated with cagE- mutants, which have a defective type IV secretion system, did not exhibit EGFR upregulation. Celecoxib had inhibitory effects on the H. pylori-induced overexpression of COX-2 (p=0.015), EGFR (p=0.025), pAkt (p=0.025), and pGSK3beta (p=0.029) by Western blot analysis.
CONCLUSIONS
H. pylori with an intact type IV secretion system activated the COX-2 and EGFR-Akt pathways in the AGS cell line. As celecoxib exhibited inhibitory effects on the EGFR signaling pathway, the cross-talk of COX-2 and EGFR likely mediates H. pylori-induced gastric cancer.

Keyword

Gastric carcinoma; Helicobacter pylori; Cyclooxygenase 2; Receptor, epidermal growth factor; Celecoxib

MeSH Terms

Blotting, Western
Cell Line
Cyclooxygenase 2
Epidermal Growth Factor
Glycogen Synthase
Helicobacter
Helicobacter pylori
Heparin
Intercellular Signaling Peptides and Proteins
Pyrazoles
Receptor, Epidermal Growth Factor
RNA, Messenger
Signal Transduction
Stomach Neoplasms
Sulfonamides
Transforming Growth Factor beta
Up-Regulation
Cyclooxygenase 2
Epidermal Growth Factor
Glycogen Synthase
Heparin
Intercellular Signaling Peptides and Proteins
Pyrazoles
RNA, Messenger
Receptor, Epidermal Growth Factor
Sulfonamides
Transforming Growth Factor beta