2016 Fiscal Year Final Research Report
Hypoxic radiosensitization by DMAG, an Hsp90 inhibitor
| Project/Area Number |
25461927
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Research Collaborator |
ASAHINA Taito
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | 低酸素細胞放射線増感 / Hｓｐ90阻害剤 / DMAG |
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| Outline of Final Research Achievements |
We investigated the radiosensitizing activity of 17-[2-(dimethylamino)ethyl]amino-17-desmethoxygeldanamycin (DMAG), an inhibitor of Hsp90, on hypoxic cells. Two human tumor cell lines, HT1080 and HeLa, were used. The radiosensitivity of cells was assessed by a standard colony-forming assay.
The exposure of HeLa cells to 100nM DMAG for 24 h significantly increased the expression of Hsp70, a marker of Hsp90 inhibition. However, there was no difference in its expression between cases with and without hypoxic treatment for 4 h. Exposure to DMAG for 24 h was slightly cytotoxic, but no further effect was observed with the additional hypoxic treatment.
DMAG at 100nM showed a weak radiosensitizing effect on both cells under oxic conditions.However, Sensitizer enhancement ratios for hypoxic HeLa and HT1080 cells were significantly greater than those for oxic cells. Western blot analysis also demonstrated that the treatment decreased the expression of HIF-1 alpha.
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| Free Research Field |
放射線科学
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