2023 Fiscal Year Final Research Report
Study of anticancer platinum dinuclear complex on transport mechanism and in vitro cytotoxicity toward oxaliplatin-resistant colorectal tumor
Project/Area Number |
19K16340
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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Research Institution | Suzuka University of Medical Science |
Principal Investigator |
UEMURA Masako 鈴鹿医療科学大学, 薬学部, 助教 (70511997)
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Project Period (FY) |
2019-04-01 – 2024-03-31
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Keywords | 白金錯体 / 抗がん剤 / 大腸がん / オキサリプラチン耐性 / 細胞内蓄積量 / トランスポーター |
Outline of Final Research Achievements |
Tetrazolato-bridged dinuclear platinum(II) complexes (tetrazolato-bridged complexes) show anti-cancer activity against several types of cancer. Therefore, they are expected to be developed as a next-generation platinum anti-cancer drugs. In this study, we revealed that organic cation transporters/Na, K-ATPases are involved in the transport of tetrazolate-bridged complexes into/out of cancer cells, respectively. In addition, we newly synthesized HCT116 human colorectal cancer cells which are resistant to oxaliplatin, and found that tetrazolate-bridged complexes and their derivatives overcome cross-resistance to oxaliplatin.
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Free Research Field |
生物無機化学
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Academic Significance and Societal Importance of the Research Achievements |
オキサリプラチンを含む白金製剤を用いた治療では、反復投与によって生じるがん細胞の耐性によって治療法の選択肢が狭められることが問題となる。本研究では、オキサリプラチン耐性がん細胞にも有効なテトラゾラト架橋錯体の創出において、さらなる構造最適化をする上で有用な知見が得られた。また、テトラゾラト架橋錯体は慢性毒性が軽度であることがすでに明らかにされているため、本研究の成果が多くの臨床的利点を兼ね備えた次世代白金製剤の創出に貢献することが期待される。
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