The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells.
OBJECTIVE
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-β (TGF-β) 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-3β (pGSK3β) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 µmol/L).


RESULTS
H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-β, 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 pGSK3β (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.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Jaeyeon
J
Kim
Nayoung
N
Kim
Ji Hyun
JH
Park
Hyun
H
Chang
Ji Yeon
JY
Kim
Dong Ho
DH
Lee
Jung Mogg
JM
Kim
Joo Sung
JS
Kim
Hyun Chae
HC
Jung
Celecoxib; Cyclooxygenase 2; Gastric carcinoma; Helicobacter pylori; Receptor, epidermal growth factor