Molecular mechanisms of radio-enhancement with the topoII target in human lung adenocarcinoma A549 cells.
| Project/Area Number |
16591196
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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 | University of Fukui |
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Principal Investigator |
HAYASHI Sachiko University of Fukui, Faculty of Medical Sciences, Assistant Professor, 医学部, 助手 (00218570)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Hideki University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (40142377)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | radio-enhancement effect / human lung adenocarcinoma A549 cells / p53 gene / DNA topoisomerase II / amrubicin (amrubicinol) / ras gene / DNA Topoisomerase II / A549細胞 / TopoII標的制癌剤 / Human Lung carcinoma A549 cells / radiosenssitivity / enhancement effect |
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| Research Abstract |
Repair of DNA damage are caused by the activity of topoisomerase II due to the mutation of ras gene, brings resistant to radiation to the cells. To overcome radiation resistance, participation of p53 gene as to the mechanisms of radio-enhancement effects were clarified on the combination therapy with radiation and four agents, amrubicin (amrubicinol), adriamycin or VP-16, of topoisomerase II target in molecular level. As a result, these agents showed the radio-enhancement effects of 1.3 times to radiation alone equally. In the kinetics of p53 induction, the p53-independent apoptosis after single or combination treatment didn't show the significant increase, but the necrosis showed that. Those findings suggested that AMR and AMROH directly inhibit DNA topoisomerase II activities without affecting the p53 cascade, in spite of the wild type. AMR and AMROH were also shown to dynamically enhance the radiosensitivity of A549 cells. Thus, for multidisciplinary anticancer therapy, the antitumor effects of radiotherapy can be improved by administering AMR or its metabolite AMROH.
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Report
(4 results)
Research Products
(6 results)
