| Project/Area Number |
18K09164
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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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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 去勢抵抗性前立腺癌 / ドセタキセル / 耐性獲得機構 / 新規治療 |
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| Outline of Final Research Achievements |
A parental human CRPC cell line, PC3 (PC3/P) was continuously exposed to increasing doses of docetaxel, and cell line resistant to docetaxel, PC3/R, was developed. There were no significant differences in sensitivities to cabazitaxel, between PC3/P and PC3/R. In PC3/P, both docetaxel and cabazitaxel markedly inhibited the expression levels of phosphorylated Akt and p44/42 MAPK. In PC3/R, however, phosphorylation of Akt and p44/42 MAPK were maintained following treatment with docetaxel, whereas treatment with cabazitaxel resulted in the marked down-regulation of phosphorylated Akt, but not that of p44/42 MAPK. Antitumor activity of cabazitaxel in CRPC cells even after the acquisition of resistance to docetaxel could be explained, at least in part, by the inactivation of Akt, persistently phosphorylated following treatment with docetaxel.
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| Academic Significance and Societal Importance of the Research Achievements |
ドセタキセルはホルモン療法に抵抗性を獲得した進行前立腺癌に対する第一選択の治療である。本研究ではドセタキセル抵抗性前立腺癌株を樹立し、その解析を行ったところ，ドセタキセル抵抗性にAktの恒常的リン酸化が重要な役割を果たしていることを明らかにし，Akt特異的阻害剤がドセタキセル抵抗性前立腺癌株のドセタキセルに対する感受性を顕著に亢進させることを示した。以上より、上記の試みが進行前立腺癌に対する新たな治療戦略になりえる可能性があると考える。
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