Development of new radiation sensitization therapy by drug repositioning of chloroquine

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07771
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Keio University
• Principal Investigator: SHIGEMATSU Naoyuki 慶應義塾大学, 医学部(信濃町), 教授 (30178868)
• Co-Investigator(Kenkyū-buntansha): 深田 淳一 慶應義塾大学, 医学部(信濃町), 講師 (50338159) ; 公田 龍一 慶應義塾大学, 医学部(信濃町), 助教 (00464834) ; 小池 直義 慶應義塾大学, 医学部(信濃町), 助教 (60464913)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 放射線生物学 / 膵癌 / 放射線抵抗性 / オートファジー

Outline of Final Research Achievements

As a treatment method for pancreatic cancer, which is an intractable malignant tumor, we focused on radiation resistance by autophagy and searched for the radiosensitizing effect of chloroquine drug repositioning. Pancreatic cancer cells were used to form spheroids, which were irradiated and administered with chloroquine in both normal medium and undernutrition, but there was no significant change in survival rate or size due to chloroquine, and no radiation sensitizing effect was observed.Moreover, the autophagy inhibitory effect was not clear. However, another study suggested an inhibitory effect on mitochondrial autophagy, mitophagy.

Free Research Field

放射線治療

Academic Significance and Societal Importance of the Research Achievements

膵癌の多くは切除不能であり、放射線治療抵抗性で予後不良であることから放射線増感効果に着目した抗腫瘍効果の増強を探索する試みは重要と考える。オートファジーに着目した放射線増感剤の探索、機序解明を進めることで、放射線生物学的にも重要な研究と考えている。
本研究ではクロロキンによる増感効果、オートファジー阻害効果を明らかにすることはできなかったが、マイトファジーの阻害作用が示唆された。