| Project/Area Number |
25462618
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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 |
Obstetrics and gynecology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
TAKENAGA MITSUKO 聖マリアンナ医科大学, 医学(系)研究科(研究院), 准教授 (10236490)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA YUKI 聖マリアンナ医科大学, 医学部, 助教 (60387066)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | KSP阻害 / キネシンモータータンパク / 細胞周期 / ヒト卵巣がん細胞 / アポトーシス / KSP / キネシンモータータンパク質 / 抗がん剤 / ヒト卵巣がん |
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| Outline of Final Research Achievements |
Among synthetic kinesin spindle protein (KSP) inhibitor compounds, KPYB10602, a six-member lactam-fused carbazole derivative was the most potent in vitro against cell growth of human ovarian cancer, A2780. KPYB10602 caused dose-dependent suppression of tumor growth in vivo. Mitotic arrest due to KPYB10602 was confirmed in vitro, and was characterized by inhibition of securin degradation. Apoptosis after mitotic arrest was associated with an increase in the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2. Increase of reactive oxygen species (ROS) and caspase pathway were also involved. Furthermore, KPYB10602 caused little neurotoxicity in vivo. Therefore, KPYB10602 could be a promising candidate as an anti-tumor agent with reduced adverse events for treating human ovarian cancer.
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