Effect of SGLT2 inhibitor for hepatocellular carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17446
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kurume University
• Principal Investigator: Nakano Dan 久留米大学, 医学部, 助教 (40723987)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肝細胞癌 / SGLT2 / SGLT2阻害剤 / 糖尿病薬

Outline of Final Research Achievements

The expression and mitochondrial localization of SGLT2 in hepatoma cell lines were revealed, and SGLT2 inhibitors suppressed the growth of hepatoma cell lines. The three main metabolic pathways that were found to be involved in this mechanism were 1) the electron transfer system, 2) the fatty acid metabolism pathway, and 3) the pyrin and pyrimidine pathway, which is a DNA synthesis pathway. The SGLT2 inhibitor also affected chemokines in hepatocellular carcinoma cell lines and was found to significantly reduce chemokines that affect hepatocellular carcinoma growth.
These findings suggest that SGLT2 inhibitors may have a growth inhibitory effect on hepatocellular carcinoma cells through both metabolic changes and microenvironmental changes caused by chemokine alterations.

Free Research Field

脂肪肝

Academic Significance and Societal Importance of the Research Achievements

肝臓癌は日本では死亡数第5位にあたる悪性腫瘍である。肝癌細胞におけるSGLTの発現およびSGLT2阻害による肝癌細胞増殖抑制およびその作用機序を解明したことで、新たな癌増殖抑制機序を発見した。また、SGLT2阻害により肝癌細胞の生存・増殖抑制効果が得られたことで、SGLT2阻害剤がすでに糖尿病薬として治療効果および安全性が確認されている薬剤であることから、直ちに臨床応用が可能な肝癌の新規治療戦略となりうる。