| RRC ID |
43907
|
| 著者 |
Miyake N, Chikumi H, Takata M, Nakamoto M, Igishi T, Shimizu E.
|
| タイトル |
Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells.
|
| ジャーナル |
Oncol Rep
|
| Abstract |
The mammalian target of rapamycin (mTOR) is a key kinase acting downstream of growth factor receptor PI3K and AKT signaling, leading to processes resulting in increased cell size and proliferation through translation control. Rapamycin, a specific inhibitor of mTOR, results predominately in G1 cell cycle arrest through translation control and occasionally, cell type-dependent apoptosis by an unknown mechanism. In this study, we investigated the effect and mechanism of action of rapamycin on non-small cell lung cancer (NSCLC) cell lines with p53 mutations. Cell proliferation was evaluated by modified MTT assay. The apoptotic effect of rapamycin was measured by caspase-3 activation and flow cytometric analysis of Annexin V binding. The expression of Bcl-2 and the release of cytochrome c from mitochondria were evaluated by western blotting. We found that rapamycin induced apoptosis in NSCLC cell lines with p53 mutations. Western blot analysis demonstrated that rapamycin downregulates the expression levels of Bcl-2, which leads to increased cytochrome c release from mitochondria and subsequent activation of caspase cascades. These findings suggest that rapamycin induces p53-independent apoptosis through downregulation of Bcl-2 and the mitochondrial pathway in NSCLC cell lines as a novel antitumor mechanism.
|
| 巻・号 |
28(3)
|
| ページ |
848-54
|
| 公開日 |
2012-9-1
|
| DOI |
10.3892/or.2012.1855
|
| PMID |
22710790
|
| MeSH |
Antibiotics, Antineoplastic / pharmacology*
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / metabolism
Carcinoma, Non-Small-Cell Lung
Caspase 3 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cytochromes c / metabolism
Humans
Lung Neoplasms
Mitochondria / metabolism*
Mutation
Sirolimus / pharmacology*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
|
| IF |
3.417
|
| 引用数 |
25
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RERF-LC-AI(RCB0444) |
