Effect of redox metabolic flux regulated by cancer metabolism on anticancer drug resistance
| Project/Area Number |
17K15673
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 2-デオキシグルコース / 膵がん細胞株 / メトホルミン / がん代謝 / 併用投与 / 相乗効果 / 抗がん剤耐性 / 抗酸化代謝物 / 2-デオキシ-D-グルコース（2DG） / 抗がん剤感受性 / MIAPaCa2 細胞 / A549細胞 / シスプラチン / N-アセチルシステイン（NAC） / 活性酸素種（ROS） / 酸化ストレス / ドライバー遺伝子 |
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| Outline of Final Research Achievements |
Many cancer cells also exert resistance to the action of anti-cancer agents because they reprogram metabolism in a glycolytic-dominant manner and respond to adverse environments. The glucose analog 2-deoxyglucose (2DG) not only inhibits glycolysis and suppresses the growth of cancer cells, but also enhances the action of drugs such as anticancer agents. In the present study, we found that 2DG synergistically enhanced the action of cisplatin or metformin on pancreatic cancer cells. It was also found that the combination of 2DG and metabolite suppressed the action of 2DG on cells. It is expected that the cancer treatment will be further advanced by further understanding the action of 2DG.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、がんが栄養の使い方を変化させてブドウ糖を多量に使うようになっている性質を利用して新しい薬の候補を調べた研究です。がん細胞がブドウ糖を使うのを防ぐ2DGという化合物を、抗がん剤などの薬（シスプラチンやメトホルミン）と一緒にがん細胞に加えると、薬の効き目が高くなることがわかりました。この飲み合わせが効果的な理由を調べることで、いろいろながんに効く薬を作るヒントを調べられる可能性があります。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Downregulation of protein disulfide-isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma2019
Author(s)
Kondo R, Ishino K, Wada R, Takata H, Peng WX, Kudo M, Kure S, Kaneya Y, Taniai N, Yoshida H, Naito Z
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Journal Title
International Journal of Oncology
Volume: 54
Pages: 1409-1421
DOI
Related Report
Peer Reviewed
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[Journal Article] 2-Deoxy-D-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells2018
Author(s)
Ishino K, Kudo M, Peng WX, Kure S, Kawahara K, Teduka K, Kawamoto Y, Kitamura T, Fujii T, Yamamoto T, Wada R, Naito Z
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Journal Title
Biochem Biophys Res Comm
Volume: 501
Issue: 3
Pages: 668-673
DOI
Related Report
Peer Reviewed / Open Access
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