Constitutive Overexpression of P-glycoprotein, Rather than Breast Cancer Resistance Protein or Organic Cation Transporter 1, Contributes to Acquisition of Imatinib-Resistance in K562 Cells

摘要: The purpose of this study was to investigate the contribution drug transporters in acquired imatinib-resistance. Specifically, we focused on efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), an influx transporter, organic cation transporter 1 (OCT1). We established imatinib-resistant K562 cells (K562/IM). Real-time PCR or Western blot analyses were performed examine mRNA levels. Alamar blue method used cytotoxicity assay. transport activities intracellular imatinib levels measured by flow cytometry HPLC, respectively. K562/IM displayed a 47-fold increase over parent cells. Both P-gp BCRP overexpressed relative K562. Furthermore, level markedly reduced K562/IM. Interestingly, cyclosporin A, inhibitor, but not fumitremorgin C, restored both imatinib-sensitivity level. By contrast, no significant difference expression function OCT1 observed between P-gp, rather than OCT1, is partially responsible for development imatinib-resistance due constitutive functional overexpression, leading accumulation