Monitoring changes in drug resistance in cancer cells using a three-dimensional pharmacokinetic system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20171
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Nagasaki University
• Principal Investigator: Miyamoto Daisuke 長崎大学, 医歯薬学総合研究科(医学系), 助教 (10845481)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 共培養 / トランスウェル / 癌細胞スフェロイド / 薬剤アッセイ

Outline of Final Research Achievements

We constructed a drug excretion system in which human hepatocytes and intestinal epithelial cells were co-cultured, and evaluated the drug response of anticancer drugs metabolized by the system against cancer cell spheroids.
Colon cancer cell lines were seeded and formed spheroid on cultured plates, and hepatocytes and intestinal epithelial cells were cultured to semi-confluence. After 24 hours of addition, the drug was metabolized through hepatocytes and intestinal epithelial cells, and on the fifth day of addition, the cells on the periphery of the cancer cell spheroid were disintegrated. These results suggest that the hepatic/intestinal transwell-mediated metabolism of the anticancer drug may reproduce the pharmacokinetics of the drug in vivo and may have different mechanisms of action of the anticancer drug.

Free Research Field

組織工学

Academic Significance and Societal Importance of the Research Achievements

近年の細胞応答性評価研究では二次元的に複数の薬物動態関連細胞を配列させた技術が報告されているものの、生体内では物質拡散等の影響を考慮する必要性がある。本研究ではトランスウェルの表面ならびに裏面に薬物動態関連細胞である肝細胞と腸管上皮細胞をそれぞれ播種することで立体的な薬剤応答性システムを開発し、薬物動態関連細胞が代謝した抗がん剤によって癌細胞スフェロイドの応答性を評価することができた。これらの結果は生体内での抗癌剤応答を模倣するものであり、今後の薬剤試験へ大きく貢献できると期待する。