2020 Fiscal Year Final Research Report
Cancer stem cell characteristics in mTOR inhibitor-resistant kidney cancer cells
Project/Area Number |
17K11121
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Urology
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Research Institution | Akita University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Keywords | 腎細胞癌 / 癌幹細胞 / mTOR阻害薬 / Aldehyde dehydrogenase |
Outline of Final Research Achievements |
Aldehyde dehydrogenase (ALDH) activity increased in a time-dependent manner, showing resistance to EVE but not 786-O PAR. Cancer stem cell characteristics were confirmed by tumor sphere-formation assay (45.8 versus 6.3, p < 0.001) and colony formation assay, which showed tolerance to irradiation (RTx) (area % of colony at 4-Gy RTx: 3.02% versus 0.55%, p = 0.01), and supported by an increase in G0/G1 phase (53.4% versus 42.0% p = 0.04) via bromodeoxyuridine assay. ALDH activity by flow cytometry showed marked increasing ALDH-positive sub-populations (28.1% versus 0.3%, p < 0.001), and inhibition of ALDH activity by disulfiram (ALDH-specific inhibitor) showed a significant decrease in cell viability .
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Free Research Field |
医学
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Academic Significance and Societal Importance of the Research Achievements |
mTORi耐性RCCにおいて癌幹細胞特性が有意に亢進していることが明らかになった。ALDHは癌幹細胞の維持する上で重要な役割を果たしており、mTORi耐性克服の標的となる可能性がある
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