| Project/Area Number |
16K11009
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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 |
Urology
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| Research Institution | Kagawa University |
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Principal Investigator |
TAOKA RIKIYA 香川大学, 医学部, 助教 (10403784)
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| Co-Investigator(Kenkyū-buntansha) |
筧 善行 香川大学, 大学本部, 学長 (20214273)
杉元 幹史 香川大学, 医学部, 教授 (10243768)
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| Research Collaborator |
Stephen Safe テキサスA&M大学, 薬理学, 教授
Kamat Ashish MDアンダーソン癌センター, 泌尿器科学, 教授
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 膀胱癌 / 活性酸素 / specificity protein / 幹細胞 / Specificity Protein / ROS / CF3DODA-Me / Stem cells / Specificity protein / 抗癌剤 / 腫瘍学 |
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| Outline of Final Research Achievements |
CF3DODA-Me is a new compound derived synthetically from licorice. In this study, we have investigated the anticancer effects of CF3DODA-Me, and determined its effects on Specificity protein (Sp) transcription factors and reactive oxygen species (ROS) activity in bladder cancer cells. In bladder cancer cells, CF3DODA-Me induced ROS, and inhibited cell viability, survival, and the expression of Sp and Sp-regulated proteins (VEGF, VEGFR2, Bcl-2, Survivin). These anticancer effects were clearly attenuated by co-treatment with antioxidant GSH. Silencing of Sp reduced Sp-regulated proteins and induced apoptosis. In bladder cancer stem cells, CF3DODA-Me downregulated Sp and Sp-regulated proteins, and inhibited sphere formation. In vivo setting, CF3DODA-Me also reduced the expression of Sp, increased amount of active caspase-3 positive cells, and inhibited tumor growth as compared to the control. These results demonstrated a novel ROS-dependent mechanism of anticancer activity for CF3DODA-Me.
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| Academic Significance and Societal Importance of the Research Achievements |
膀胱癌は、既存の抗癌剤に加え免疫チェックポイント阻害剤が導入され、手術や放射線療法を組み合わせたMulti-Modal Therapyが積極的に行われる現在においても未だ満足できる治療アウトカムを得ていない。本研究で用いたCF3DODA-Meは、膀胱癌に対し十二分な抗腫瘍効果を発揮する薬剤で、既存治療薬と異なる作用機序も想定されることから、導入する治療戦略スペースは必ず存在する。本研究の結果は、膀胱癌で悩まれる多くの患者の福音になる可能性を秘めるほか、ROSの新たな抗腫瘍メカニズムを示すもので、社会的・学術的意義は非常に大きい。
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