| Project/Area Number |
18K06793
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
Ogihara Takuo 高崎健康福祉大学, 薬学部, 教授 (80448886)
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| Co-Investigator(Kenkyū-buntansha) |
矢野 健太郎 高崎健康福祉大学, 薬学部, 講師 (40644290)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | P-糖タンパク / 上皮間葉転換 / 排出系トランスポーター / 転写調節因子 / ERMタンパク質 / mRNA / Snail / 免疫沈降法 / 足場タンパクERM / MRP5 / BCRP / HCC827細胞 / HepG2細胞 / P-gp / 足場タンパク / EMT / 薬物耐性 / 肺がん / エンチノスタット / 薬剤耐性 / 浸潤と転移 / がん多剤耐性 |
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| Outline of Final Research Achievements |
We analyzed the functional changes of efflux transporters such as P-glycoprotein(P-gp) and their scaffold proteins, ERM(Ezrin, Radixin, Moesin) during the induction of epithelial-mesenchymal transition (EMT) in cancer metastasis using the transcriptional regulator, Snail. The protein and mRNA expression levels of Moesin and Radixin were increased in human lung cancer-derived HCC827 and human liver cancer-derived HepG2 cells, respectively, indicating that P-gp function was enhanced. The mRNA level of P-gp was not increased, but only the membrane expression level was increased. The interaction between P-gp and Radixin, an ERM was investigated by immunoprecipitation, and Radixin was found to interact with P-gp. In HCC827, where the Snail gene was introduced, it was suggested that the expression and function of the efflux transporter MRP5 were enhanced.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、がん細胞において Snail 誘発性の EMT が生じる際に，ERMの発現増加に伴って排出系トランスポーター，特にP-gpの細胞膜発現が増加し，その機能が上昇することが確認された。またこのとき、発現が増加する ERM タンパク質は臓器毎に異なる可能性が示唆された。今回の検討により，がん多剤耐性は抗がん剤の曝露をきっかけとするだけでなく，がんの転移の際にも起こりえることが示唆され，さらにP-gpを細胞膜上に固定する足場タンパクは組織ごとに異なることから，組織特異的な抗がん薬の開発に繋がるものと期待される．
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