2015 Fiscal Year Final Research Report
The involvement of mitochondrial membrane potential in cross-resistance between radiation and docetaxel
| Project/Area Number |
25340026
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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 |
Risk sciences of radiation and chemicals
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 放射線耐性 / ドセタキセル耐性 / ミトコンドリア / ROS / ρ0細胞 |
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| Outline of Final Research Achievements |
To understand the molecular mechanisms underlying cancer cell radioresistance, we established clinically relevant radioresistant (CRR) cells that continue to proliferate during exposure to 2 Gy/day X-rays for more than 30 days. A modified high-density survival assay for anticancer-drug screening revealed that CRR cells were resistant to an anti-microtubule agent, docetaxel (DTX). After treatment with DTX or exposure to X-rays reactive oxygen species from mitochondria (mtROS) were generated in parental cells but not in CRR cells, suggesting that the involvement of mtROS in the cross-resistance to DTX and X-rays. Mitochondrial membrane potential was lower in CRR cells than that in parental cells. Depletion of mtDNA induced DTX resistance in parental cells. In the present study, novel DTX resistant mechanism was found by investigating CRR cells and ρ0 cells which lack mitochondrial DNA.
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| Free Research Field |
放射線基礎医学
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