2021 Fiscal Year Final Research Report
Role of rho0 phenotype on acquisition of gemcitabine resistance in pancreatic ductal carcinoma
| Project/Area Number |
19K16564
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 膵管癌 / ゲムシタビン / 薬剤耐性 / ミトコンドリアDNA / 部分ρ０形質 / 酸化的リン酸化 / 活性酸素種 |
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| Outline of Final Research Achievements |
The gemcitabine-resistant cell line established by continuous gemcitabine treatment had a partial ρ0 phenotype, indicating a partial deletion in mitochondrial DNA. These cells acquired gemcitabine resistance by suppressing gemcitabine-induced mitochondrial ROS production through reduction of mitochondrial membrane potential and inhibition of oxidative phosphorylation by gemcitabine treatment. Thus, it was suggested that acquisition of the partial ρ0 phenotype due to DNA toxicity of the anticancer drug itself plays an important role in anticancer drug resistance. It is hoped that more effective chemotherapy will be realized by investigating therapies that target this partial ρ0 phenotype.
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| Free Research Field |
人体病理学
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| Academic Significance and Societal Importance of the Research Achievements |
癌細胞における抗がん剤耐性の獲得に、抗がん剤の有するミトコンドリアDNAに対する毒性に起因する部分ρ０形質の獲得が重要な役割を果たすことが示された。この結果は、抗癌剤による化学療法そのものが耐性を惹起する内在的危険性を有することを、その機序を明らかにしたものであり、重要な知見と考えられる。今後は部分ρ０形質の獲得の抑制、あるいは、部分ρ０形質を克服する治療法を開発することにより、抗がん剤耐性の獲得を抑制し、より効果的な化学療法を可能にすることが可能になると期待される。
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