| RRC ID |
10916
|
| 著者 |
Luo JC, Chi CW, Lin HY, Chang FY, Lu CL, Chen CY, Lee SD.
|
| タイトル |
Dexamethasone inhibits epidermal growth factor-stimulated gastric epithelial cell proliferation.
|
| ジャーナル |
J Pharmacol Exp Ther
|
| Abstract |
Epidermal growth factor (EGF) is essential to heal gastric ulcers, whereas glucocorticoid delays rat gastric ulcer healing. We found that dexamethasone inhibited EGF-stimulated rat gastric epithelial cell (RGM-1) proliferation by cell count and DNA synthesis analysis of flow cytometry and attempted to elucidate the possible mechanistic pathway via Western blot analysis. EGF (10 ng/ml) treatment for 24 h significantly increased RGM-1 cell proliferation, and dexamethasone (10(-8) and 10(-6) M) markedly suppressed EGF-stimulated cell proliferation. Western blotting results demonstrated that the phosphorylated extracellular signal-regulated kinase (pERK) (pERK1/pERK2) significantly increased at 10 min after EGF treatment. This was followed by increase of cyclooxygenase (COX)-2 expression at 3 h after EGF treatment. The continued increase of COX-2 (up to 18 h) resulted in increased intracellular prostaglandin E(2) and cyclin D1 expression significantly after 8 and 12 h of EGF treatment. Dexamethasone substantially reduced EGF-stimulated COX-2 expression at 3 and 6 h and cyclin D1 expression at 8 and 12 h. Pretreatment of RGM-1 cells with dexamethasone or 2'-amino-3'-methoxyflavone (PD98059)-mitogen-activated protein kinase kinase inhibitor (5 x 10(-5) M) significantly reduced EGF-stimulated pERK1/pERK2 expression. Simultaneous treatment of RGM-1 cells with PD98059 and EGF also markedly decreased EGF-stimulated COX-2 expression at 6 h. These findings indicate that dexamethasone significantly suppresses EGF-stimulated gastric epithelial cell proliferation, and one of the pathways involved is via inhibiting activation of ERK1/ERK2, followed by inhibition of COX-2, cyclin D1 expression, and finally DNA synthesis.
|
| 巻・号 |
320(2)
|
| ページ |
687-94
|
| 公開日 |
2007-2-1
|
| DOI |
10.1124/jpet.106.113035
|
| PII |
jpet.106.113035
|
| PMID |
17077316
|
| MeSH |
Animals
Cell Proliferation / drug effects
Cells, Cultured
Cyclooxygenase 2 / metabolism
Dexamethasone / pharmacology*
Epidermal Growth Factor / antagonists & inhibitors*
Extracellular Signal-Regulated MAP Kinases / metabolism
Flavonoids / pharmacology
Gastric Mucosa / cytology
Gastric Mucosa / drug effects*
Nitrobenzenes / pharmacology
Phosphorylation
Rats
Signal Transduction / drug effects
Sulfonamides / pharmacology
p38 Mitogen-Activated Protein Kinases / metabolism
|
| IF |
3.561
|
| 引用数 |
21
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
RGM1(RCB0876) |
