FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells
The overexpression of P-glycoprotein (P-gp/ABCB1) is a major contributor to multidrug resistance (MDR). Therefore, identifying effective drugs to counteract ABCB1-mediated MDR is essential. FRAX486, a p21-activated kinase (PAK) inhibitor, was the focus of this study, which aimed to determine if it could reverse ABCB1-mediated MDR and to explore its mechanism of action. The CCK8 assay showed that FRAX486 significantly reversed MDR mediated by ABCB1. Additionally, western blot and immunofluorescence analyses demonstrated that FRAX486 did not affect the expression or intracellular localization of ABCB1. Importantly, FRAX486 increased intracellular drug accumulation and decreased drug efflux, leading to the reversal of MDR. Docking studies further revealed a strong affinity between FRAX486 and ABCB1. This research underscores the potential of FRAX486 to counteract ABCB1-mediated MDR and offers valuable insights for its clinical use.