論文 - 詳細
| RRC ID | 42059 |
|---|---|
| 著者 | Wong BC, Jiang XH, Lin MC, Tu SP, Cui JT, Jiang SH, Wong WM, Yuen MF, Lam SK, Kung HF. |
| タイトル | Cyclooxygenase-2 inhibitor (SC-236) suppresses activator protein-1 through c-Jun NH2-terminal kinase. |
| ジャーナル | Gastroenterology |
| Abstract |
BACKGROUND AND AIMS:Aspirin exerts antitumor effect partly through blocking tumor promoter-induced activator protein-1 (AP-1) activation. The aim of this study is to determine how specific COX-2 inhibitor SC-236 mediates antitumor effect by modulation of AP-1-signaling pathway. METHODS:AP-1 transcriptional activity and DNA-binding activity were detected by luciferase reporter assay and gel shift assay, separately. Mitogen-activated protein kinase (MAPK) activation was determined by Western blot and in vitro kinase assay. Antisense oligonucleotide against c-Jun-N-terminal kinase (JNK) was used to suppress JNK expression. RESULTS:We showed that SC-236 inhibited 12-O-tetradecanoylphorbol-13-acetate (PMA)-induced cell transformation in a dose-dependent manner in JB6 cells. At a dose range (12.5-50 micromol/L) that inhibited cell transformation, SC-236 also inhibited anchorage-independent cell growth and AP-1-activation in 3 gastric cancer cells, independent of COX-prostaglandin synthesis. SC-236 down-regulated c-Jun-NH2-terminal kinase phosphorylation and activity. Suppression of JNK activity reversed the inhibitory effect on AP-1 activity by SC-236 and suppressed gastric cancer cell growth, indicating that the inhibitory effect of SC-236 on AP-1 activation and cell growth was through interaction with JNK. CONCLUSIONS:The inhibitory effect on JNK-c-Jun/AP-1 activation contributes to the antitumor effect of COX-2-specific inhibitor, and inhibition of JNK activation may have a therapeutic benefit against gastric cancer. |
| 巻・号 | 126(1) |
| ページ | 136-47 |
| 公開日 | 2004-1-1 |
| DOI | 10.1053/j.gastro.2003.10.063 |
| PII | S0016508503017311 |
| PMID | 14699495 |
| MeSH | Cell Division / drug effects Cell Line, Tumor Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / administration & dosage Cyclooxygenase Inhibitors / pharmacology* Dinoprostone / antagonists & inhibitors Dose-Response Relationship, Drug Enzyme Activation / physiology Humans Isoenzymes / antagonists & inhibitors* JNK Mitogen-Activated Protein Kinases Membrane Proteins Mitogen-Activated Protein Kinases / antagonists & inhibitors* Phosphorylation / drug effects Prostaglandin-Endoperoxide Synthases Pyrazoles / administration & dosage Pyrazoles / pharmacology* Stomach Neoplasms / pathology Sulfonamides / administration & dosage Sulfonamides / pharmacology* Tetradecanoylphorbol Acetate / pharmacology Transcription Factor AP-1 / antagonists & inhibitors* |
| IF | 17.373 |
| 引用数 | 44 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |