Project/Area Number |
26460231
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | Tohoku Medical and Pharmaceutical University |
Principal Investigator |
YOMOGIDA Shin 東北医科薬科大学, 薬学部, 准教授 (80230845)
|
Co-Investigator(Kenkyū-buntansha) |
染谷 明正 順天堂大学, 医学部, 准教授 (90167479)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | がん細胞 / 抗がん剤耐性 / Keap1 / Nerf2 / プロテオソーム / P-糖タンパク質 / Nrf2 / 薬剤耐性 / オートファジー / ADPリボシル化因子 / DNAマイクロアレイ |
Outline of Final Research Achievements |
Keap1-Nrf2 pathway plays a critical role in the protection of cells against several stresses. P-glycoprotein (Pgp) transports a broad range of anticancer drugs out of the cells. We examined whether Keap1-Nrf2 pathway may affect the expression of Pgp using the Doxorubicin-resistant K562 cells. Keap1 level in the cytosolic fraction decreased in the abundantly expressing Pgp cell. Interestingly, Keap1 level in the cytosolic fraction was increased in the weakly expressing Pgp cell. Whereas, the expression of Nrf2 in the cytosolic fraction was not detected, Nrf2 level in the membrane-bound organellar fraction was alike in Keap1. The resistant cells treated with MG-132 were investigated for Keap1 and Narf2 level. Keap1 level in the cytosolic fraction was not changed. However, Keap1 level in the membrane-bound organellar fraction increased. Collectively, these observations suggest that Keap1-Nrf2 pathway may be involved in the expression of Pgp.
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