| Project/Area Number |
26460496
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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 |
Experimental pathology
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| Research Institution | Nihon University |
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Principal Investigator |
SANO Makoto 日本大学, 医学部, 兼任講師 (70339323)
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| Co-Investigator(Kenkyū-buntansha) |
宮入 伸一 日本大学, 薬学部, 教授 (50209855)
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| Co-Investigator(Renkei-kenkyūsha) |
HOMMA Taku 日本大学, 医学部, 准教授 (00307852)
SAITO Hiroki 日本大学, 薬学部, 助教 (30385976)
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| Research Collaborator |
LEWIS Brian
ICHIMARU Yoshimi
HIROTANI Yukari
UCHIDA Kei
BEZEHA Marina
NAGATANI Yukie
WATANABE Mayu
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵管癌 / トランスジェニックマウス / 新薬開発 / トランスレーショナルリサーチ / 浸潤性膵管癌 / インディルビン誘導体 / 移植モデル / KPCマウス / 抗腫瘍効果 / p-CDK1/Cyclin B1抑制 / G2/M arrest / アポトーシス誘導 / モデルマウス / 創薬開発 / 遺伝子改変マウスモデル |
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| Outline of Final Research Achievements |
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. To identify effective anti-cancer drugs for PDAC, we established a screening system based on spheroid formation. We found that indirubin 3'-oxime (Indox) and 5-methoxyindirubin 3'-oxime (5MeOIndox) inhibited PDAC cell proliferation. Furthermore, PDAC xenograft growth was also inhibited in BALB/c nu/nu mice after administration of Indox and 5MeOIndox. Both phosphorylated CDK1 and cyclin B1 levels in PDAC cells were significantly reduced by treatment with Indox and 5MeOIndox in vitro and in vivo. Cell cycle analysis revealed that 5MeOIndox, but not Indox, induced G2/M arrest. Annexin V-propidium iodide double-staining analysis demonstrated that Indox induced abundant non-apoptotic cell death of PDAC cells, while 5MeOIndox predominantly induced early apoptosis. These results suggest that one mechanism of 5MeOIndox is to induce G2/M arrest of PDAC cells via inhibition of CDK1/cyclin B1 levels, thereby leading to apoptosis.
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