2. Academic Validation
  3. FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells

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

  • Braz J Med Biol Res. 2024 Jul 1:57:e13357. doi: 10.1590/1414-431X2024e13357.
Meng Zhang 1,  Xiaoqi Zeng 1,  Meiling She 2,  Xingduo Dong 3,  Jun Chen 1,  Qingquan Xiong 1,  Guobin Qiu 1,  Shuyi Yang 1,  Xiangqi Li 4,  Guanghui Ren 1
Affiliations

Affiliations

  • 1 Department of Thyroid and Breast Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China.
  • 2 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
  • 3 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, USA.
  • 4 Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong, China.
PMID: 38958364 DOI: 10.1590/1414-431X2024e13357
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.

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