論文 - 詳細
| RRC ID | 36767 |
|---|---|
| 著者 | Horibe S, Matsuda A, Tanahashi T, Inoue J, Kawauchi S, Mizuno S, Ueno M, Takahashi K, Maeda Y, Maegouchi T, Murakami Y, Yumoto R, Nagai J, Takano M. |
| タイトル | Cisplatin resistance in human lung cancer cells is linked with dysregulation of cell cycle associated proteins. |
| ジャーナル | Life Sci |
| Abstract |
AIMS:Cisplatin (CDDP) is a platinum-based drug that is widely used in cancer chemotherapy, but the development of resistance in tumor cells is a major weakness of these treatments. Several mechanisms have been proposed to explain cisplatin resistance, and disruption of certain cellular pathways could modulate drug sensitivity to cisplatin. A lower level of cross-resistance to cisplatin leads to better outcomes in clinical use. MAIN METHODS:Cross-resistance was assessed using cisplatin resistant lung cancer cell line A549/CDDP. Cell cycle analysis was used to examine the effect of cisplatin on cell signaling pathways regulating G2/M transition in cisplatin resistant cells. KEY FINDINGS:A549/CDDP cells exhibited cross-resistance to carboplatin, but not oxaliplatin, which is often found in platinum analogues. Flow cytometry showed that nocodazole treatment caused a G2/M block in both A549/CDDP cells and cisplatin susceptible cells. However, A549/CDDP cells escaped the G2/M block following exposure to cisplatin. Activation of the Cdc2/CyclinB complex is required for transition from G2 to M phase, and the inactive form of phosphorylated Cdc2 is activated by Cdc25C dephosphorylation of Tyr15. In the cisplatin-treated susceptible cells, the levels of phosphorylated Cdc2 and Cdc25C were markedly decreased, leading to a loss of Cdc2 activity and G2/M arrest. In A549/CDDP cells, however, Cdc2 activity was supported by the expression of Cdc2 and Cdc25C after the addition of cisplatin, which resulted in G2/M progression. SIGNIFICANCE:The resistance phenotype of G2/M progression has been correlated with dysregulation of Cdc2 in a human lung cancer cell line selected for cisplatin. |
| 巻・号 | 124 |
| ページ | 31-40 |
| 公開日 | 2015-3-1 |
| DOI | 10.1016/j.lfs.2015.01.011 |
| PII | S0024-3205(15)00050-8 |
| PMID | 25625243 |
| MeSH | Antineoplastic Agents / pharmacology* CDC2 Protein Kinase Cell Cycle Proteins / metabolism Cell Division / drug effects Cell Line, Tumor Cisplatin / pharmacology* Cyclin-Dependent Kinases / metabolism* Drug Resistance, Neoplasm G2 Phase / drug effects G2 Phase Cell Cycle Checkpoints / drug effects Humans Lung Neoplasms / drug therapy* Lung Neoplasms / pathology M Phase Cell Cycle Checkpoints Nocodazole / pharmacology Organoplatinum Compounds / pharmacology* Oxaliplatin Phosphorylation / drug effects Signal Transduction / drug effects |
| IF | 3.647 |
| 引用数 | 24 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | A549 |