| Project/Area Number |
26670566
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
SAITO KATSUYO 高崎健康福祉大学, 薬学部, 助手 (90455288)
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| Co-Investigator(Kenkyū-buntansha) |
村上 孝 埼玉医科大学, 医学部, 教授 (00326852)
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| Co-Investigator(Renkei-kenkyūsha) |
KOBAYASHI Yasuhiko 国立研究開発法人量子科学技術研究開発機構, 放射線生物応用研究部, 部長 (50354957)
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| Research Collaborator |
FUNAYAMA Tomoo 国立研究開発法人量子科学技術研究開発機構, 放射線生物応用研究部, 上席研究員 (40354956)
YOKOTA Yuichiro 国立研究開発法人量子科学技術研究開発機構, 放射線生物応用研究部, 主幹研究員 (30391288)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 重粒子線 / 重粒子線治療 / エピジェネティック / ヒストン脱アセチル化酵素阻害剤 / HDAC阻害剤 / HDACi / 増感 / 併用効果 / 増感剤 / 感受性 / エピジェネティック制御 / DNA二本鎖切断 / イメージング |
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| Outline of Final Research Achievements |
Malignant melanoma is one of the representative types of refractory tumors and the most lethal form of cancer, resisting not only chemotherapy but also radiotherapy. In this study, we examined whether histone deacetylase inhibitors (HDACis) can be used to sensitize malignant melanoma B16F10 cells to carbon ion irradiation. The cells were first treated with HDACis (FK228, trichostatin A, valproic acid and vorinostat) and were then exposed to two types of radiation (carbon ions and gamma-rays). We found that HDACis enhanced the radiation-induced apoptosis and suppression of clonogenicity that was induced by irradiation, having a greater effect with carbon ion irradiation than with gamma-rays. Carbon ion irradiation and the HDACi treatment induced G2/M and G0/G1 arrest, respectively. Based on these findings, we propose that pretreatment with HDACis as radiosensitizers to induce G1 arrest combined with carbon ion irradiation may have clinical efficacy in refractory cancer patients.
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