The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells
- Title
- The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells
- Author
- 김정목
- Keywords
- Gastric carcinoma; Helicobacter pylori; Cyclooxygenase 2; Receptor, epidermal growth factor; Celecoxib
- Issue Date
- 2013-09
- Publisher
- EDITORIAL OFFICE GUT & LIVER, 305 LOTTE GOLD ROSE II, 890-59, DAECHI 4-DONG, GANGNAM-GU, SEOUL, 135-839, SOUTH KOREA
- Citation
- The Editorial Office of Gut and Liver
- 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-3 beta (pGSK3 beta) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 mu mol/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 pGSK3 beta (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.
- URI
- https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001802446http://hdl.handle.net/20.500.11754/44520
- ISSN
- 1976-2283
- DOI
- 10.5009/gnl.2013.7.5.552
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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