2. Academic Validation
  3. Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells

Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells

  • Biochem Biophys Res Commun. 2024 Jan 8:691:149314. doi: 10.1016/j.bbrc.2023.149314.
Chao Zhang 1,  Min-Na Huang 2,  Jun-Qi Shan 3,  Zun-Jie Hu 4,  Zi-Wei Li 5,  Jian-Ying Liu 6
Affiliations

Affiliations

  • 1 Department of Urology Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Jinan, Shandong, 250117, PR China.
  • 2 Dalton Cardiovascular Research Center, Department of Medical Pharmacology and Physiology, University of Missouri, School of Medicine, 134 Research Park Dr, Columbia, MO, 65211, USA.
  • 3 Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Jinan, Shandong, 250117, PR China.
  • 4 Department of Urology Surgery, The Affiliated Taian City Central Hospital of Qingdao University, No. 29 Longtan Road, Taian, Shandong, 271000, PR China.
  • 5 Department of Experimental Center, Shandong University of Traditional Chinese Medicine, No. 4655 Daxue Road, Changqing, Jinan, Shandong, 250355, PR China. Electronic address: 60011972@sdutcm.edu.cn.
  • 6 Department of Nuclear Medicine, The Third Affiliated Hospital of Shandong First Medical University, No. 38 Wuyingshan Road, Tianqiao, Jinan, Shandong, 250031, PR China. Electronic address: liujianying@sdfmu.edu.cn.
PMID: 38039831 DOI: 10.1016/j.bbrc.2023.149314
Abstract

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.

Keywords

ABC transporter; ABCB1; FGFR inhibitor; Multidrug resistance; Pemigatinib.

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