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2016 Fiscal Year Final Research Report

Identification of new anti-cancer drug for microenvironment in pancreatic cancer using KPC mouse

Research Project

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Project/Area Number 26460496
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionNihon University

Principal Investigator

SANO Makoto  日本大学, 医学部, 兼任講師 (70339323)

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)
Research Collaborator LEWIS Brian  
ICHIMARU Yoshimi  
HIROTANI Yukari  
UCHIDA Kei  
BEZEHA Marina  
NAGATANI Yukie  
WATANABE Mayu  
Project Period (FY) 2014-04-01 – 2017-03-31
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
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.

Free Research Field

実験病理学

URL: 

Published: 2018-03-22  

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