Identification of new pathway on expression of P-glycoprotein in the doxorubicin resistance of K562 human leukemia cells

2016 Fiscal Year Final Research Report

• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

生化学、タンパク質の機能解析