| Project/Area Number |
23791751
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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 |
Urology
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| Research Institution | Mie University |
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Principal Investigator |
ISHII Kenichiro 三重大学, 大学院・医学系研究科, 助教 (90397513)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 前立腺癌 / 癌関連線維芽細胞 / ナフトピジル / オフターゲット効果 / 前立腺肥大症治療薬 / ケミカルバイオロジー / 再燃前立腺癌 / 癌間質 / 初代培養 |
|---|
| Research Abstract |
In the tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are considered to play a critical role in the promotion of tumorigenesis. Recently, we have reported that the antiproliferative effect of naftopidil is not related to androgen sensitivity of the cells or the ? 1-adrenoceptor subtype expression in prostate cancer cells, suggesting that naftopidil has an off-target effect for various types of cells. To identify the cellular signal targets of naftopidil in CAFs, we used the SCADS inhibitor kits including more than 320 chemicals. Our results demonstrated that inhibitors against GSK-3 and CDK showed the similar effects with naftopidil in PCaSC-8. In addition, western blot analysis showed that the decreases of GSK-3 phosphorylation and CDK2 abundance were observed in naftopidil-treated cells. Finally, we suggest that GSK-3 and CDK2 might be important targets for induction of G1 cell cycle arrest by naftopidil treatment.
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