New drug discovery screening targeting autophagy

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15621
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: NAKATA Kohei 九州大学, 大学病院, 助教 (30419569)
• Co-Investigator(Kenkyū-buntansha): 白羽根 健吾 九州大学, 医学研究院, 共同研究員 (10529803) ; 当間 宏樹 九州大学, 医学研究院, 共同研究員 (80437780) ; 冨永 洋平 九州大学, 医学研究院, 共同研究員 (90304823)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: オートファジー / 膵星細胞 / 創薬 / 膵癌

Outline of Final Research Achievements

Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor microenvironment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. We have recently reported regarding the relationships between autophagy and activation of the PSCs and found that autophagy inhibition in PSCs reduced the activation of PSC and proliferation of PSC, followed by the inhibition of the invasiveness of pancreatic cancer cells in vitro and vivo (Endo et al, gastroenterology, 2017). Based on these results we performed high-throughput screening in Drug Discovery for pancreatic cancer targeting pancreatic stellate cells. We found several candidates, which may inhibit the PSCs activation. We also validated and found the compound X truly inhibited PSCs activation and also found it inhibited the proliferation of PSCs.

Free Research Field

医歯薬学