The mechanisms by which RIG-I-like receptor pathways modulate cellular radiation response
| Project/Area Number |
18K07623
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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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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | RIG-I / ミトコンドリア / 放射線増感 / アポトーシス / Fas / DAP3 / RIG-I様受容体 / Fasリガンド / 放射線 / 細胞死 / IFN-β / 放射線治療 |
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| Outline of Final Research Achievements |
Although we found that agonist of RIG-I-like receptor (RLR) enhances radiation-induced cell killing effect in human lung cancer cells, it remains unknow the mechanisms. In the present project, we demonstrated that RLR agonist enhances radiosensitivity of lung cancer cells by decreasing mitochondrial ribosome protein DAP3 that regulates cellular radioresistance of lung cancer cells. In addition, we showed that additional treatment with apoptosis-inducing agent Fas ligand enhanced antitumor effects against the lung cancer cells co-treated with RLR agonist and ionizing radiation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，RLRの刺激因子による放射線感受性制御機構の解明に取り組み，ミトコンドリアリボソームタンパク質DAP3がヒト肺癌細胞の放射線抵抗性を制御すること，RLR刺激因子がDAP3の発現低下を介して細胞の放射線応答を制御していることを世界で初めて明らかにした。放射線応答におけるミトコンドリア関連因子の新たな役割を示すことができたため，本成果の学術的意義は高いと考える。加えて，ヒト肺癌細胞に対する放射線増感の標的や放射線致死効果を高めるための新たな戦略を見出すことができたため，本研究は放射線治療の発展に資する社会的意義のある研究であったと考える。
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Report
(4 results)
Research Products
(30 results)
