論文 - 詳細
| RRC ID | 67785 |
|---|---|
| 著者 | Inoue M, Yoshimura M, Kobayashi M, Morinibu A, Itasaka S, Hiraoka M, Harada H. |
| タイトル | PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase. |
| ジャーナル | Sci Rep |
| Abstract |
The cytotoxicity of ionizing radiation depends on the cell cycle phase; therefore, its pharmacological manipulation, especially the induction of cell cycle arrest at the radiosensitive mitotic-phase (M-phase), has been attempted for effective radiation therapy. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that functions in mitotic progression, and is now recognized as a potential target for radiosensitization. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating cell cycle phases of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. The TAK-960 treatment exhibited radiosensitizing effects in vitro, especially when it increased the proportion of M-phase cells. TAK-960 did not sensitize cancer cells to radiation when an insufficient amount of time was provided to induce mitotic arrest. The overexpression of a PLK1 mutant, PLK1-R136G&T210D, which was confirmed to cancel the TAK-960-mediated increase in the proportion of mitotic cells, abrogated the radiosensitizing effects of TAK-960. A tumor growth delay assay also demonstrated that the radiosensitizing effects of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis for targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatments. |
| 巻・号 | 5 |
| ページ | 15666 |
| 公開日 | 2015-10-27 |
| DOI | 10.1038/srep15666 |
| PII | srep15666 |
| PMID | 26503893 |
| PMC | PMC4621528 |
| MeSH | 4-Aminobenzoic Acid / therapeutic use Animals Apoptosis / drug effects Azepines / therapeutic use* Cell Cycle Proteins / antagonists & inhibitors* Cell Cycle Proteins / genetics Cell Line, Tumor Cell Proliferation / drug effects HCT116 Cells HeLa Cells Humans M Phase Cell Cycle Checkpoints / drug effects* M Phase Cell Cycle Checkpoints / genetics Mice Mice, Inbred BALB C Mice, Nude Mitosis / genetics Neoplasms / radiotherapy* Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / genetics Proto-Oncogene Proteins / antagonists & inhibitors* Proto-Oncogene Proteins / genetics Radiation Tolerance / drug effects* Radiation Tolerance / genetics Radiation-Sensitizing Agents / therapeutic use* Xenograft Model Antitumor Assays |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa/Fucci(RCB2812) |