The influence of anticancer drug on the expression of transporters

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Keio University
• Principal Investigator: Akiyoshi Takeshi 慶應義塾大学, 薬学部(芝共立), 講師 (50399143)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: トランスポーター / 抗がん剤曝露 / 絶対定量プロテオミクス解析

Outline of Final Research Achievements

The aim of this study was to evaluate the expression level of pharmacokinetics-related transporters and endogenous substance transport transporters in rats exposed to the irinotecan which caused severe intestinal damage.
The plasma membrane fraction of the tissues, such as small intestine, liver, and kidney were prepared from irinotecan-exposed rats. After trypsin digestion, the expression level of each transporter-specific peptide in the samples was measured by absolute quantitative proteomic analysis using LC-MSMS.
As a result, significant expression changes were observed in P-glycoprotein as well as in endogenous substance transport transporters. These results suggest that the exposure of irinotecan may affect the pharmacokinetics of substrate of transporter.

Free Research Field

臨床薬物動態学

Academic Significance and Societal Importance of the Research Achievements

臨床上ではイリノテカンなどの抗がん剤投与時に様々なトランスポーター基質薬が併用投与される。本研究により、イリノテカン時にはP糖蛋白質の発現、特に、小腸における発現量が有意に変動したことから、ジゴキシンやダビガトランなど臨床上重要なトランスポーター基質薬の吸収量の変動が示唆れれる。さらに、本研究においては、内因性物質である胆汁酸の輸送に寄与するトランスポーター発現量の有意な変動も明らかになった。これらの変動は、最終的には様々な疾患発症のリスクを示唆しており、今後これらの臨床上の影響の程度を評価する必要がある。