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Biochem Biophys Res Commun ; 691: 149314, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38039831

RESUMEN

P: -glycoprotein (P-gp/ABCB1) overexpression is one of the primary causes of multidrug resistance (MDR). Therefore, it is crucial to discover effective pharmaceuticals to combat multidrug resistance mediated by ABCB1. Pemigatinib is a selective the fibroblast growth factor receptor (FGFR) inhibitor that is used to treat a variety of solid tumors, Clinical Trials for Urothelial Carcinoma (NCT02872714) completed its research on Pemigatinib. This study aimed to determine whether Pemigatinib can reverse ABCB1-mediated multidrug resistance, as well as its mechanism of action. Pemigatinib substantially reversed ABCB1-mediated multidrug resistance, as determined by a CCK8 assay, and immunofluorescence experiments revealed that Pemigatinib had no effect on the intracellular localization of ABCB1. Pemigatinib was discovered to increase intracellular drug accumulation, thereby reversing multidrug resistance. In addition, Docking analysis revealed that Pemigatinib and ABCB1 have a high affinity for one another. This study concludes that Pemigatinib is capable of reversing the multidrug resistance mediated by ABCB1, offering ideas and references for the clinical application of Pemigatinib.


Asunto(s)
Antineoplásicos , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Resistencia a Antineoplásicos , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos , Subfamilia B de Transportador de Casetes de Unión a ATP
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