2014 Fiscal Year Final Research Report
| Project/Area Number |
24791293
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
YOSHIMURA MICHIO 京都大学, 医学(系)研究科(研究院), 助教 (40597936)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 放射線増感 / 分子標的薬 / 放射線治療 / 細胞周期 |
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| Outline of Final Research Achievements |
Polo-like kinase 1 is a serine/threonine kinase that functions in mitotic progression. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating the cell cycle phase of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. In vitro clonogenic assays as well as time-lapse imaging and flow cytometric analyses of cell cycle phases demonstrated that the TAK-960 treatment exhibited a radiosensitizing effect, especially when it increased the proportion of M-phase cells. Tumor growth delay assay combined with optical imaging of cell cycle phases in tumor xenografts also demonstrated that the radiosensitizing effect of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis of targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatment.
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| Free Research Field |
放射線治療
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