A basic research for novel treatment for castration resistant prostate cancer via LSD1 and autophagy
| Project/Area Number |
16K11023
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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 | Nagoya City University |
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Principal Investigator |
ETANI TOSHIKI 名古屋市立大学, 大学院医学研究科, 助教 (30600754)
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| Co-Investigator(Kenkyū-buntansha) |
河合 憲康 名古屋市立大学, 大学院医学研究科, 准教授 (20254279)
内木 綾 名古屋市立大学, 大学院医学研究科, 高度医療教育研究センター講師 (20509236)
安藤 亮介 名古屋市立大学, 大学院医学研究科, 講師 (30381867)
飯田 啓太郎 名古屋市立大学, 大学院医学研究科, 臨床研究医 (30713945)
安井 孝周 名古屋市立大学, 大学院医学研究科, 教授 (40326153)
内木 拓 名古屋市立大学, 大学院医学研究科, 講師 (50551272)
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| Research Collaborator |
TAKAHASHI satoru
SUZUKI takayoshi
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | LSD1 / エピゲノム / 前立腺癌 / アポトーシス / p21 / LSD1発現変化 / オートファジー / 去勢抵抗性前立腺癌 / 癌 / 細胞・組織 / マイクロアレイ |
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| Outline of Final Research Achievements |
The CRPC cell lines, 22Rv1, PC3, and PCai1CS, were treated with NCL1, and LSD1 expression and cell viability were assessed. CRPC cells showed strong LSD1 expression, and cell viability was decreased by NCL1 in a dose-dependent manner. In western blotting and flow cytometry, NCL1 also dose-dependently induced caspase-dependent apoptosis. In addition, stimulation of autophagy was observed in NCL1-treated 22Rv1 cells by transmission electron microscopy and LysoTracker analysis. In ex vivo analysis, castrated nude mice were injected subcutaneously with PCai1 cells and intraperitoneally with NCL1. Tumor volume was found to be reduced with no adverse effects in NCL1-treated mice compared with controls. Finally, immunohistochemical analysis using consecutive human specimens in pre- and post-androgen deprivation therapy demonstrated that LSD1 expression levels in CRPC were very high, and identical to levels observed in previously examined prostate biopsy specimens.
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| Academic Significance and Societal Importance of the Research Achievements |
前立腺癌は世界で最も多くみられるがんの一つとなり、本邦でもその発生は増加の一途をたどっている。前立腺癌は初期治療に抵抗性となると治癒が困難となり、新規治療法の開発が強く望まれている。私たちはエピゲノム酵素のひとつであるLSD1のその治療標的としての意義に着目し、各種の泌尿器癌で研究を進めてきた。本研究は、これまでの去勢感受性前立腺癌へのLSD1阻害剤の効果の研究に引き続き、臨床でももっとも問題となる去勢抵抗性前立腺癌へのLSD1阻害剤の効果を明らかにした報告であり、LSD1阻害剤およびオートファジー阻害剤の前立腺癌新規治療法としての可能性を大きく推進するものであると考えられる。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses castration-resistant prostate cancer growth via regulation of apoptosis and autophagy.2019
Author(s)
Etani T, Naiki T, Naiki-Ito A, Suzuki T, Iida K, Nozaki S, Kato H, Yagayasu Y, Suzuki S, Kawai N, Yasui T, Takahashi S.
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Journal Title
J Clin Med.
Volume: 8
Issue: 4
Pages: 442-442
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Novel selective lysine‐specific demethylase 1 inhibitors and autophagy inhibitors effectively impair castration‐resistant prostate cancer growth.2016
Author(s)
Etani Toshiki, Naiki Taku, Suzuki Takayoshi, Nagai Takashi, Iida Keitaro, Ando Ryosuke, Kawai Noriyasu, Tozawa Keiichi, Mogami Tohru, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2016
Place of Presentation
San Diego, USA
Year and Date
2016-05-06
Related Report
Int'l Joint Research
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