The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells
Gut and Liver
;
: 552-559, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-103741
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Pirazóis
/
Neoplasias Gástricas
/
Sulfonamidas
/
RNA Mensageiro
/
Heparina
/
Transdução de Sinais
/
Regulação para Cima
/
Linhagem Celular
/
Western Blotting
/
Fator de Crescimento Transformador beta
Idioma:
Inglês
Revista:
Gut and Liver
Ano de publicação:
2013
Tipo de documento:
Artigo
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