Development of hybrid therapy using iron chelators and regenerative therapy for advanced hepatocellular carcinoma with decompensated liver cirrhosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08358
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Takami Taro 山口大学, 大学院医学系研究科, 教授 (60511251)
• Co-Investigator(Kenkyū-buntansha): 山本 直樹 山口大学, 教育・学生支援機構, 教授 (90448283) ; 松本 俊彦 山口大学, 大学院医学系研究科, 講師 (70634723) ; 藤澤 浩一 産業医科大学, 産業生態科学研究所, 教授 (00448284)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝硬変症 / 肝細胞癌 / 鉄キレート剤 / 間葉系幹細胞

Outline of Final Research Achievements

In rats fed with choline-deficient L-amino acid-defined diet, developing cirrhosis with liver tumors, iron chelator treatment tended to suppress the tumor development, but further investigation of the effects of MSCs including MSC passages was necessary. On the other hand, in the iron chelator-resistant cancer cell line, an increase in lactate production was caused by a metabolic shift to the glycolytic pathway, showing that the anti-tumor effect of iron chelator was enhanced when the lactate concentration in the cancer microenvironment was lower. Therefore, these results suggest that MSCs may have a novel effect of suppressing the glycolytic shift of hepatocellular carcinoma cells in liver cirrhosis.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

肝臓領域のアンメット・メディカルニーズのひとつは「分子標的薬投与ができない肝予備能不良例(Child-Pugh B)における切除不能進行肝細胞癌」である。今回、ラット肝発癌肝硬変モデルおよび細胞共培養系により鉄キレート剤の抗腫瘍メカニズムを検証することができ、新たなMSC抗腫瘍機序を想起することができ、今後のハイブリッド療法の開発につながる。