有機カチオン輸送系を介した白金系抗がん剤の腎毒性発現機構

概要

論文の詳細を見る
Platinum agents are widely used in cancer chemotherapy. Cisplatin, carboplatin, oxaliplatin and nedaplatin have a common chemical structure consisting of platinum, carrier groups and leaving groups, and undergo the similar mechanism of cytotoxicity. Only cisplatin induces nephrotoxicity, although the molecular mechanism involved is unclear. Organic cation transporter (OCT)/SLC22A, and multidrug and toxin extrusion (MATE)/SLC47A play a role in renal handling of cationic drug in the kidney. We focused on a role of transporters in nephrotoxicity of platinum agents. OCT2 mediates the transport of cisplatin and is the determinant of cisplatin-induced nephrotoxicity. In addition, MATE1 protects cisplatin-induced nephrotoxicity. Oxaliplatin, which was a superior substrate of the luminal efflux transporter, MATE2-K as well as OCT2, did not show nephrotoxicity. Moreover, carboplatin and nedaplatin were not transported by these transporters. Substrate specificity could regulate the features of platinum agents. Recent findings indicate that organic cation transporters are key to the nephrotoxicity of platinum agents.