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XIAP and P-glycoprotein co-expression is related to imatinib resistance in chronic myeloid leukemia cells
Authors:Karina Lani Silva  Paloma Silva de Souza  Gabriela Nestal de Moraes  Arthur Moellmann-Coelho  Flavia da Cunha Vasconcelos  Raquel Ciuvalschi Maia
Institution:1. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Coordenação Geral Técnico-Científica (CGCT), Instituto Nacional de Câncer (INCA) and Programa de Pós-Graduação em Oncologia/INCA, Brazil;2. Serviço de Hematologia, Hospital do Câncer I, INCA, Brazil
Abstract:P-glycoprotein (Pgp) and XIAP co-expression has been discussed in the process of the acquisition of multidrug resistance (MDR) in cancer. Here, we evaluated XIAP and Pgp expression in chronic myeloid leukemia (CML) samples, showing a positive correlation between them. Furthermore, we evaluated the effects of imatinib in XIAP and Pgp expression using CML cell lines K562 (Pgp) and K562-Lucena (Pgp+). Imatinib increased XIAP and Pgp expression in K562-Lucena cells, while in K562 cells a downregulation of these proteins was observed, suggesting that imatinib induces an increment of MDR phenotype of CML cells that previously exhibit high levels of Pgp/XIAP co-expression.
Keywords:CML  chronic myeloid leukemia  Pgp  P-glycoprotein  MDR  multidrug resistance  IAPs  inhibitor of apoptosis proteins  RFI  ratio of mean of fluorescence intensity  MFI  mean of fluorescence intensity  Rho-123  rhodamine-123  CSA  cyclosporin A  VRP  verapamil  IC50  concentration achieving 50% inhibition of cell growth
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