論文 - 詳細
| RRC ID | 43675 |
|---|---|
| 著者 | Shimokawa T, Seike M, Soeno C, Uesaka H, Miyanaga A, Mizutani H, Kitamura K, Minegishi Y, Noro R, Okano T, Yoshimura A, Gemma A. |
| タイトル | Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS:We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. RESULTS:We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. CONCLUSION:Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules. |
| 巻・号 | 106(5) |
| ページ | 867-75 |
| 公開日 | 2012-2-28 |
| DOI | 10.1038/bjc.2012.7 |
| PII | bjc20127 |
| PMID | 22333600 |
| PMC | PMC3305973 |
| MeSH | Antineoplastic Agents / pharmacology* Antineoplastic Agents / therapeutic use Cell Line, Tumor Cell Proliferation / drug effects Drug Resistance, Neoplasm Gene Expression Profiling Humans Indoles / pharmacology* Indoles / therapeutic use Janus Kinase 1 / antagonists & inhibitors Janus Kinase 1 / metabolism* Lung Neoplasms / drug therapy* Lung Neoplasms / genetics Lung Neoplasms / metabolism Lung Neoplasms / pathology MAP Kinase Signaling System / drug effects* MicroRNAs / metabolism Protein Kinase Inhibitors / pharmacology Protein Serine-Threonine Kinases / antagonists & inhibitors* |
| IF | 5.791 |
| 引用数 | 13 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RERF-LC-KJ(RCB1313) RERF-LC-AI(RCB0444) LC-2/ad(RCB0440) LC-1/sq(RCB0455) LC-1F(RCB0439) MS-1(RCB0725) |