Anti-tumor effect against hepatoma cells by suppressing the Warburg effect by AMPK activation and GSK3 inhibition

• Project/Area Number: 15K09012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagasaki University
• Principal Investigator: NAKAO Kazuhiko 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00264218)
• Co-Investigator(Kenkyū-buntansha): 玉田 陽子 長崎大学, 病院(医学系), 助教 (70393460)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝癌細胞 / ワールブルグ効果 / AMPK / GSK3 / 肝細胞癌 / GSK3β / 微小環境変化

Outline of Final Research Achievements

Hepatoma cells are already in a metabolic state predominantly related to glycolysis in the normal state. Under hypoxic conditions as well as hyperglycemia / hyperglycemia / hyperinsulin culture conditions, it was further metabolized to a glycolytic dominant state in agreement with the induction of HIF-1. At this time, it became clear that the kinase activity of AMPK is suppressed in a time-dependent manner. In addition, it was observed that the addition of metformin, an AMPK activating agent, returned the metabolic state shifted predominantly to the glycolysis system under normal culture conditions. It was confirmed that expression of epithelial mesenchymal transition-related genes induced under hypoxic conditions and under hyperglycemia / hyperglycemia culture conditions was also suppressed by the addition of metformin.