The inhibition of hepatocellular carcinoma growth through Warburg effect disruption using cell-size regulating gene

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K09431
• 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: Miuma Satoshi 長崎大学, 病院(医学系), 講師 (30437892)
• Co-Investigator(Kenkyū-buntansha): 山本 一男 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (70255123)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肝細胞癌 / ワールブルグ効果 / Largen遺伝子

Outline of Final Research Achievements

Hepatocellular carcinoma (HCC) is still refractory, and the development of new therapy is required. In this study, we examined the suppressive effect of genes that increase cell size (Largen) on HCC for developing new therapies.
First, we created transgenic mice having Largen and examined whether the HCC development was suppressed or not in these mice. HCC development was suppressed significantly compared to normal mouse. Next, metabolome analysis was performed to elucidate the mechanism, which revealed that the suppression was caused by dramatic changes of metabolism in tumor tissue induced by Largen expression. Similar results were obtained in in vitro experiments using HCC cell lines. Our results suggest that Largen might be very useful to suppress the development of HCC. In the future, the development of novel tumor metabolism inhibitors targeting Largen is expected.

Free Research Field

肝細胞癌

Academic Significance and Societal Importance of the Research Achievements

学術的意義：細胞のサイズは細胞にとって非常に適切に調整されており、これらは癌細胞においても同様である。癌細胞を少し大きくすることにより、癌細胞代謝、癌周囲環境は劇的に変化し、癌細胞は生存することができなくなる。本研究ではこれらのことを明らかにした。
社会的意義：癌代謝は新たな創薬のターゲットになると考えられる。さらに研究を継続し、将来的には癌代謝を標的とする新たな治療法を開発する必要がある。