| Project/Area Number |
16591185
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Gunma University |
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Principal Investigator |
AKIMOTO Tetsuo GUNMA UNIVERSITY, Dept.Radiation Oncology, Assistant Professor, 医学部, 講師 (10261851)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Molecular target / Radiosensitivity / Radiation therapy / Enhahcement effect / signal transduction / 放射線 |
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| Research Abstract |
The purpose of this project is to explore the molecular targets for potentiation of radiation-induced cell killing in various cancer cells. In regarding molecular targets for potentiation of radiosensitivity in prostate cancer cells, we obtained following results.
In hormone sensitive prostate cancer, DHT at a concentration of 1 nM caused enhancement of the proliferative activity and reduction of the radiosensitivity of the cells. Radicicol at a concentration of 500 nM abolished the DHT-induced decrease in cellular radiosensitivity and potentiated the radiation-induced cell killing synergistically. Consistent with the changes in the cellular radiosensitivity, radicicol degraded AR, Raf-1 and HER2/neu via reduced binding of AR to Hsp90, although selective degradation of HER2/neu caused by Herceptin, a monoclonal antibody against HER2, did not affect the cellular radiosensitivity. However, DHT did not change proliferative activity and radiosensitivity of hormone-independent prostate cancer cells (PC3). Radicicol at a concentration of 500 nM enhanced radiation-induced cell killing synergistically. In underlining mechanism, inhibition of survival signal transduction pathway such as PI3K-Akt pathways was closely associated with enhancement of radiation-induced cell killing in hormone-independent prostate cancer cells. The results suggest that the Hsp90 chaperone complex may be a potential molecular target for potentiation of radiation-induced cell killing in both hormone- sensitive and hormone-independent prostate cancer cell line.
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