Metabolic reprogramming and its mechanism by nucleosides in cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Ueda Kumiko 神戸薬科大学, 薬学部, 講師 (10309437)
• Co-Investigator(Kenkyū-buntansha): 大河原 賢一 神戸薬科大学, 薬学部, 教授 (30291470)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: ヌクレオシド / 解糖系 / 増殖 / トランスポーター

Outline of Final Research Achievements

Nucleosides such as adenosine are translocated into and out of human colon cancer cells via equilibrative nucleoside transporter 1 (ENT1). When ENT1 was inhibited by nitrobenzylthioinosine, an ENT1 inhibitor, or expression of ENT1 was suppressed by ENT1 siRNA treatment, glucose uptake and lactate production were observed in these cells, indicating that glycolysis was enhanced in these cells. These enhancements were accompanied by higher mRNA expressions of not only enzymes for glycolysis, but also a glucose transporter and an amino acid transporter. In these circumstances, cell proliferation was also suppressed. These findings suggest that ENT1 inhibition or ENT1 knockdown might cause metabolic reprogramming in human colon cancer cells.

Free Research Field

薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究成果より、核酸トランスポーターのがん細胞での働きの一部が明らかになったとともに、核酸トランスポーターががんの代謝リモデリングと関わっている可能性が示唆された。さらには、核酸トランスポーターの発現量低下が代謝拮抗薬の耐性と関係することを示す報告も存在することから、これらの知見は代謝拮抗薬の耐性克服に関する方策を見出すための一助となる可能性が示されたとともに、今後の新たながん治療に対して有用な知見となる可能性が示唆されたと考えられる。