論文 - 詳細
| RRC ID | 42625 |
|---|---|
| 著者 | Fan XM, Jiang XH, Gu Q, Ching YP, He H, Xia HH, Lin MC, Chan AO, Yuen MF, Kung HF, Wong BC. |
| タイトル | Inhibition of Akt/PKB by a COX-2 inhibitor induces apoptosis in gastric cancer cells. |
| ジャーナル | Digestion |
| Abstract |
BACKGROUND/AIM:Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway. METHODS:Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line. RESULTS:SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases. CONCLUSION:One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c. |
| 巻・号 | 73(2-3) |
| ページ | 75-83 |
| 公開日 | 2006-1-1 |
| DOI | 10.1159/000092747 |
| PII | 92747 |
| PMID | 16641552 |
| MeSH | Acridine Orange Adenocarcinoma / pathology* Apoptosis / drug effects* Blotting, Western Caspases / metabolism Cyclooxygenase 2 Inhibitors / pharmacology* Cytochromes c / metabolism Down-Regulation Enzyme Activation Humans Mitogen-Activated Protein Kinases / metabolism Proto-Oncogene Proteins c-akt / antagonists & inhibitors* Pyrazoles / pharmacology* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Stomach Neoplasms / pathology* Sulfonamides / pharmacology* Transfection Tumor Cells, Cultured |
| IF | 2.692 |
| 引用数 | 17 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN28(RCB1000) |