Organ-specific inactivation of cancer multidrug resistance by regulating membrane scaffold proteins

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08078
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: Ogihara Takuo 高崎健康福祉大学, 薬学部, 教授 (80448886)
• Co-Investigator(Kenkyū-buntansha): 矢野 健太郎 高崎健康福祉大学, 薬学部, 助教 (40644290)
• Co-Investigator(Renkei-kenkyūsha): Arakawa Hiroshi 金沢大学, 医薬保健研究域薬学系, 助教 (40709028) ; Idota Yoko 高崎健康福祉大学, 薬学部, 研究員 (90629594)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: P-gp / BCRP / MRPｓ / 網羅的な阻害 / 足場タンパク / がん組織 / 排出系トランスポーター / 多剤耐性

Outline of Final Research Achievements

Efflux transporters, as exemplified by P-glycoprotein (P-gp), are localized at the plasma membrane and excrete many therapeutic drugs from the cytoplasm to outside the cells. These transporters are therefore known as a major contributing factor resulting in multidrug resistance of cancer cells. Our study indicated that the regulation of transporters by scaffold proteins, such as ezrin, radixin and moesin (ERM proteins) is different between cancerous tissues. Moreover, these regulatory properties are the same as those of the corresponding normal tissues, and suggest that organ-specific differences in the regulation of P-gp by ERM proteins are retained in cancerous tissues. Furthermore, in tissues such as lung cancer, several efflux transporters were controlled by the same one scaffold protein. Therefore, it was suggested that the suppression of a specific scaffold protein comprehensively inactivated efflux transporters in certain kinds of cancerous tissue.

Free Research Field

生物薬剤学、薬物動態学