Drug screening targeting pancreatic stellate cell activation

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• 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 / スクリーニング / 新規膵癌治療薬

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.

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。

Research Products

• [Journal Article] Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix (2018)
  • Author(s): Okumura T, Ohuchida K, Kibe S, Iwamoto C, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Sada M, Horioka K, Mochidome N, Arita M, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M
  • Journal Title: Int J Cancer Volume: 144 Issue: 6 Pages: 1401-1413
  • DOI: 10.1002/ijc.31775
  • Peer Reviewed / Open Access
• [Presentation] ナノ粒子DDSを用いた新規膵星細胞活性化抑制剤の開発 (2020)
  • Author(s): 松本奏吉、仲田興平、関維雨、相良亜希子、池永直樹、大内田研宙、大塚隆生、中村雅史
  • Organizer: 第75回日本消化器外科学会総会
• [Presentation] 膵癌微小環境の制御に着目した新規膵癌治療薬剤の探索 (2020)
  • Author(s): 相良亜希子、仲田興平、山下智大、関維雨、松本奏吉、伊達聡美、池永直樹、大内田研宙、大塚隆生、中村雅史
  • Organizer: 第75回日本消化器外科学会総会
• [Presentation] Efficient Targeted Therapy for Pancreatic Cancer Using Nanosystem and Focusing on the Suppression of Pancreatic Stellate Cell Activation (2020)
  • Author(s): Matsumoto S, Nakata K, Ikenaga N, Date S, Guan W, Sagara A, Ohuchida K, Ohtsuka T, Nakamura M
  • Organizer: 14th World Congress of International Hepeto-Pancreato-Biliary Association
  • Int'l Joint Research
• [Presentation] Repositioning of Duloxetine as a New Drug for Targeting Pancreatic Cancer Microenvironment (2019)
  • Author(s): Sagara A, Nakata K, Yamashita T, Guan W, Matsumoto S, Date S, Ohtsubo Y, Shinkawa T, Kimura R, Fujii A, Ando Y, Iwamoto C, Watanabe Y, Shindo K, Ikenaga N, Moriyama T, Ohuchida K, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: The 50th Annual Meeting of the American Pancreatic Association(APA)
  • Int'l Joint Research
• [Presentation] A Novel Target That Required for Autophagy, Associated With Activation of Pancreatic Stellate Cells, Promotes Pancreatic Cancer Progression (2019)
  • Author(s): Guan W, Nakata K, Ohuchida K, Sagara A, Endo S, Ando Y, Yan Z, Matsumoto S, Shinkawa T, Ohtsubo Y, Iwamoto C, Moriyama T, Ikenaga N, Shindo K, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: The 50th Annual Meeting of the American Pancreatic Association(APA)
  • Int'l Joint Research
• [Presentation] A new investigation of drug repurposing using for duloxetine as targeting pancreatic cancer microenvironment (2019)
  • Author(s): Sagara A, Nakata K, Yamashita T, Matsumoto S, Ohotsubo Y, Shinkawa T, Shindo K, Moriyama T, Ohuchida K, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: Digestive Disease Week 2019
  • Int'l Joint Research
• [Presentation] AUTOPHAGY INHIBITION ENHANCES ANTIPROLIFERATIVE EFFECT OF SALINOMYCIN IN PANCREATIC CANCER CELLS (2019)
  • Author(s): Sagara A, Nakata K, Endo S, Matsumoto S, Ohtsubo Y, Shinkawa Tomohiko S, Shindo K, Moriyama T, Ohuchida K, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: Digestive Disease Week 2019
  • Int'l Joint Research
• [Presentation] 膵癌微小環境の制御に着目した既存薬剤を用いた膵癌治療の新たな展開 (2019)
  • Author(s): 相良亜希子、仲田興平、山下智大、松本奏吉、大坪慶志輝、新川智彦、安藤陽平、大内田研宙、大塚隆生、中村雅史
  • Organizer: 第74回日本消化器外科学会総会
• [Presentation] 膵癌細胞のオートファジー抑制は、サリノマイシンによる増殖抑制効果を増強する (2019)
  • Author(s): 相良亜希子、仲田興平、遠藤翔、大坪慶志輝、新川智彦、松本奏吉、米永晃子、安藤陽平、岐部晋、中山宏道、武居晋、進藤幸治、森山大樹、大内田研宙、大塚隆生、水元一博、中村雅史
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] Endo180 Expression and Histologic Categorization in Cancer Stroma is an Independent Prognostic Index in Pancreatic Cancer. (2018)
  • Author(s): Koikawa K, Ohuchida K, Yonenaga A, Sagara A, Ando Y, Kibe S, Takesue S,Nakayama H, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: 49th Annual Meeting of the APA
  • Int'l Joint Research
• [Presentation] オートファジー抑制は、サリノマイシンによる膵癌細胞増殖抑制効果を増強する (2018)
  • Author(s): 相良亜希子、仲田興平、遠藤翔、米永晃子、安藤陽平、岐部晋、中山宏道、武居晋、進藤幸治、森山大樹、宮坂義浩、大内田研宙、大塚隆生、水元一博、中村雅史
  • Organizer: 第49回日本膵臓学会大会
• [Patent(Industrial Property Rights)] オートファジー阻害剤及び抗癌剤 (2020)
  • Inventor(s): 仲田興平
  • Industrial Property Rights Holder: 仲田興平
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-178556
  • Filing Date: 2020