2020 Fiscal Year Final Research Report

Drug screening targeting pancreatic stellate cell activation

Research Project

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Project/Area Number	18H02880
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Kyushu University
Principal Investigator	NAKATA Kohei 九州大学, 大学病院, 講師 (30419569)
Co-Investigator(Kenkyū-buntansha)	宮坂義浩九州大学, 医学研究院, 共同研究員 (40507795) 森泰寿九州大学, 大学病院, 助教 (50632642) 大内田研宙九州大学, 大学病院, 講師 (20452708) 進藤幸治九州大学, 大学病院, 助教 (00788432) 池永直樹九州大学, 大学病院, 助教 (90759755) 貞苅良彦九州大学, 大学病院, 助教 (80784503)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	膵癌 / 膵星細胞 / 癌間質相互作用 / オートファジー / 化合物スクリーニング
Outline of Final Research Achievements	The purpose of this study is to discover the new compound targeting for pancreatic cancer microenvironment. We developed new high-throughput screening platform that can quantify PSC activation. Drug library containing FDA approved drugs was screened by this platform, and candidate compounds selected from this screening suppressed the PSCs activation, and invasion of cancer cells by disrupting tumor-stromal interactions. In vivo testing in xenograft models showed that candidate compound suppressed tumor growth; this suppression was significantly increased when combined with gemcitabine. This screening system may be useful to discover new compounds that attenuate PSC activation.
Free Research Field	医歯薬学
Academic Significance and Societal Importance of the Research Achievements	本研究で得られた候補化合物は、今後膵癌の間質標的治療の新しい候補化合物となりうる可能性が示唆された。ま本研究で開発したスクリーニングシステムは、膵星細胞の活性化抑制剤の開発のみならず、オートファジー抑制剤の同定にも応用可能と考えられる。