Correlation between molecularly targeted therapy and circadian clock in hepatocellular carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08312
• 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: Sapporo Medical University
• Principal Investigator: akutsu noriyuki 札幌医科大学, 医学部, 講師 (50531191)
• Co-Investigator(Kenkyū-buntansha): 佐々木 茂 札幌医科大学, 医学部, 准教授 (10305229) ; 仲瀬 裕志 札幌医科大学, 医学部, 教授 (60362498)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 分子標的治療 / 時計遺伝子

Outline of Final Research Achievements

The cDNA was prepared using cancerous tissue and normal tissue surrounding the cancer in cases of hepatocellular carcinoma. The expression of PER1 and PER2 was significantly lower in non-cancers compared to cancers. We analyzed the expression of Clock, Bmal1, Per1, Per2, and Cry1 using cDNA from several hepatocellular carcinoma cell lines. Cytokines were added to hepatocellular carcinoma cell lines to examine changes in the clock genes. IL6 and TNFα expression was higher in cell lines of low Per2 expression compared to those of high Per2 expression. Hep3B was mixed with 1 micro M of lenvatinib and incubated at 37°C for 48 hours. We found that the expression of clock genes was altered in several genes.

Free Research Field

肝細胞癌

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌において、癌部と非癌部で時計遺伝子に差があることがわかり、さらにいくつかのサイトカインが影響を受けることが分かった。また、分子標的治療薬で時計遺伝子の変化があることがわかった。これらのことは、肝細胞癌においても時計遺伝子の発現解析を用いることで、治療薬剤の選択や有効な投与方法に関わる可能性があり、今後さらに検討を進めていく。