論文 - 詳細
| RRC ID | 39963 |
|---|---|
| 著者 | Zhou XM, Wong BC, Fan XM, Zhang HB, Lin MC, Kung HF, Fan DM, Lam SK. |
| タイトル | Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. |
| ジャーナル | Carcinogenesis |
| Abstract |
Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer. |
| 巻・号 | 22(9) |
| ページ | 1393-7 |
| 公開日 | 2001-9-1 |
| DOI | 10.1093/carcin/22.9.1393 |
| PMID | 11532860 |
| MeSH | Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Apoptosis / drug effects* Apoptosis / physiology Aspirin / pharmacology* Caspase 3 Caspase Inhibitors Caspases / biosynthesis Caspases / genetics Cell Division / drug effects Cell Division / physiology Gene Expression Regulation, Neoplastic Humans Indomethacin / pharmacology* Membrane Proteins / biosynthesis* Membrane Proteins / genetics Poly(ADP-ribose) Polymerases / biosynthesis Poly(ADP-ribose) Polymerases / genetics Proto-Oncogene Proteins / biosynthesis* Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins c-bcl-2 / biosynthesis Proto-Oncogene Proteins c-bcl-2 / genetics Stomach Neoplasms / genetics Stomach Neoplasms / metabolism Stomach Neoplasms / pathology* Tumor Cells, Cultured Up-Regulation / drug effects bcl-2 Homologous Antagonist-Killer Protein bcl-2-Associated X Protein bcl-X Protein |
| IF | 4.603 |
| 引用数 | 99 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN28(RCB1000) |