Development of a novel therapy for hepatocellular carcinoma using short-chain fatty acids/GPR41 derived from intestinal bacteria

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17395
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Fukui
• Principal Investigator: Nishikawa Yudai 福井大学, 学術研究院医学系部門(附属病院部), 医員 (30835773)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 短鎖脂肪酸 / プロピオン酸 / 酪酸 / アポトーシス

Outline of Final Research Achievements

The purpose of this study was to elucidate the molecular mechanism of the antitumor effect of short-chain fatty acids/GPR41 signaling. HepG2 cells, cultured hepatocellular carcinoma cells, were treated with various short-chain fatty acids, and LD concentrations in the supernatant were measured. The results showed that sodium butyrate significantly increased the LD levels in the supernatant. Significant increases in levels of cleaved caspase 3 were also observed with sodium propionate and sodium butyrate. In addition, significant increases in p38 and JNK phosphorylation were observed with sodium butyrate. These results suggest that sodium butyrate induces apoptosis via the MAPKinase pathway.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

腸内細菌叢より産生され，体内に生理的に存在する短鎖脂肪酸が，肝癌培養細胞において抗腫瘍効果を発揮し，そのアポトーシス作用はMAPKinase経路を介して誘導されることが示唆された．これより腸内細菌叢への介入が肝細胞癌に対する新規治療法の一つとなる可能性を考えた．