Involvement of mitochondria in cancer cell radioresistance
| Project/Area Number |
16K00538
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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 Medical and Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | がん / 放射線抵抗性 / ミトコンドリア / 分割照射 / 放射線療法 / ρ0細胞 / 電子伝達系 / 放射線耐性 / 活性酸素 / ドセタキセル / ミトコンドリアDNA / X線 / 電離放射線 / メタボローム |
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| Outline of Final Research Achievements |
To understand the molecular mechanisms of cancer cell radioresistance, we have established clinically relevant radioresistant (CRR) cells which continue to proliferate under exposure to 2 Gy/day of X-rays for more than 30 days in vitro and in vivo. Reduction of mitochondrial membrane potential of CRR cells was observed same as mitochondrial DNA depleted ρ0 cells. The mitochondria of CRR cells was fragmented suggesting that functional mitochondrial network was disrupted. The dysfunction of mitochondria observed in CRR and ρ0 cells contribute to X-ray and docetaxel cross-resistance. However, ρ0 cells, including HeLa-R-ρ0 cells established from HeLa-R CRR cells, did not show resistance to 2 Gy/day of X-rays. CRR cells cultured under hypoxia died out within 15 days with or without 2 Gy/day of X-rays. These results strongly suggested that mitochondria play a role in CRR phenotype.
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| Academic Significance and Societal Importance of the Research Achievements |
放射線療法はがんの三大治療法の一つである。放射線に抵抗性を示すがん細胞の存在は、放射線療法の克服すべき課題の一つである。本研究では、ミトコンドリアががんの放射線抵抗性に関与していることを明らかにした。このことは、より有効な放射線療法を開発する上で重要な発見である。また、低酸素下のがん細胞は放射線に抵抗性になることが知られているものの、本研究で使用する臨床的放射線耐性細胞は低酸素下で培養すると死滅した。このことは、新規の放射線抵抗性に関するメカニズムを示唆するものであり、学術的に意義深い。本研究は、ミトコンドリアを標的とする放射線化学療法の開発に結び付く可能性があり、社会的に意義深い。
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Circulating miRNA-1290 as a potential biomarker for response to chemoradiotherapy and prognosis of patients with advanced oral squamous cell carcinoma: A single-center retrospective study2019
Author(s)
Hikaru Nakashima, Ryoji Yoshida, Akiyuki Hirosue, Kenta Kawahara, Junki Sakata, Hidetaka Arita, Tatsuro Yamamoto, Ryo Toya, Ryuji Murakami, Akimitsu Hiraki, Masanori Shinohara, Takaaki Ito, Yoshikazu Kuwahara, Hideki Nakayama
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Journal Title
Tumor Biology
Volume: 41
Pages: 1-10
Related Report
Peer Reviewed
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[Journal Article] Data on the aquaporin gene expression differences among ρ0, clinically relevant radioresistant, and the parental cells of human cervical cancer and human tongue squamous cell carcinoma.2018
Author(s)
Takashi Y, Tomita K, Kuwahara Y, Nabika H, Igarashi K, Nagasawa T, Kurimasa A, Fukumoto M, Nishitani Y, Sato T.
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Journal Title
Data Brief.
Volume: 15;20
Pages: 402-410
DOI
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Peer Reviewed / Open Access
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[Journal Article] Gene expression analyses of the small intestine of pigs in the ex-evacuation zone of the Fukushima Daiichi Nuclear Power Plant.2017
Author(s)
Morimoto M, Kato A, Kobayashi J, Okuda K, Kuwahara Y, Kino Y, Abe Y, Sekine T, Fukuda T, Isogai E, Fukumoto M.
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Journal Title
BMC Vet Res.
Volume: 13
Issue: 1
Pages: 337-337
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The causal relation between DNA damage induction in bovine lymphocytes and the Fukushima nuclear power plant accident.2016
Author(s)
Nakamura AJ, Suzuki M, Redon CE, Kuwahara Y, Yamashiro H, Abe Y, Takahashi S, Fukuda T, Isogai E, Bonner WM, Fukumoto M.
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Journal Title
Radiation Research
Volume: 印刷中
Issue: 5
Pages: 161-168
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] がんの治療抵抗性・感受性を制御する細胞膜酸化状態とALOXの関与2019
Author(s)
富田 和男, 桑原 義和, 五十嵐 健人, 髙 裕子, 長澤 大成, 並河 英紀, 田中 康一, 北中 純一, 北中 順惠, 竹村 基彦, 西山 信好, 福本 学, 西谷 佳浩, 栗政 明弘, 佐藤 友昭
Organizer
第92回 日本薬理学会年会
Related Report
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[Presentation] Sensitivity for hydrogen peroxide in ρ0 cells and involvement of membrane status2018
Author(s)
Yuko Takashi, Kazuo Tomita, Yoshikazu Kuwahara, Sayuri Yamanishi, Hideki Nabika, Koh-ich Tanaka, Junichi Kitanaka, Nobue Kitanaka, Motohiko Takemura, Nobuyoshi Nishiyama, Shouichi Miyawaki, Yoshihiro Nishitani, Tomoaki Sato
Organizer
18th World Congress of Basic and Clinical Pharmacology
Related Report
Int'l Joint Research
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[Presentation] Analysis of oxidative stress response in clinically relevant radioresistant cells2018
Author(s)
Kazuo Tomita, Yoshikazu Kuwahara, Yuko Takashi, Sayuri Yamanishi, Hideki Nabika, Koh-ich Tanaka, Junichi Kitanaka, Nobue Kitanaka, Motohiko Takemura, Nobuyoshi Nishiyama, Shouichi Miyawaki, Manabu Fukumoto, Yoshihiro Nishitani, Akihiro Kurimasa, Tomoaki Sato
Organizer
18th World Congress of Basic and Clinical Pharmacology.
Related Report
Int'l Joint Research
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[Presentation] 福島原発警戒区域内で採取されたブタ・イノブタ・イノシシの消化管における遺伝子発現解析.2017
Author(s)
森本 素子, 加藤 彩佳, 小林 仁, 奥田 圭, 桑原 義和, 木野 康志, 阿部 靖之, 関根 勉, 福田 智一, 磯貝 恵美子, 福本 学.
Organizer
第160回日本獣医学会学術集会
Related Report
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