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FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells

Authors :
Meng Zhang
Xiaoqi Zeng
Meiling She
Xingduo Dong
Jun Chen
Qingquan Xiong
Guobin Qiu
Shuyi Yang
Xiangqi Li
Guanghui Ren
Source :
Brazilian Journal of Medical and Biological Research, Vol 57 (2024)
Publication Year :
2024
Publisher :
Associação Brasileira de Divulgação Científica, 2024.

Abstract

The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.

Details

Language :
English
ISSN :
1414431X and 1414431x
Volume :
57
Database :
Directory of Open Access Journals
Journal :
Brazilian Journal of Medical and Biological Research
Publication Type :
Academic Journal
Accession number :
edsdoj.2822698d56194bf1845e291b61ac846c
Document Type :
article
Full Text :
https://doi.org/10.1590/1414-431x2024e13357