XIAP and P-glycoprotein co-expression is related to imatinib resistance in chronic myeloid leukemia cells

Leuk Res. 2013 Oct;37(10):1350-8. doi: 10.1016/j.leukres.2013.06.014. Epub 2013 Jul 25.

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; CSA; Chronic myeloid leukemia; IAPs; IC(50); Imatinib; MDR; MFI; Multidrug resistance; P-glycoprotein; Pgp; RFI; Rho-123; Survivin; VRP; XIAP; chronic myeloid leukemia; concentration achieving 50% inhibition of cell growth; cyclosporin A; inhibitor of apoptosis proteins; mean of fluorescence intensity; multidrug resistance; ratio of mean of fluorescence intensity; rhodamine-123; verapamil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Benzamides / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Child
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Leukemic / drug effects
  • Gene Expression*
  • Gene Knockdown Techniques
  • Humans
  • Imatinib Mesylate
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Male
  • Middle Aged
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / pharmacology*
  • RNA Interference
  • Survivin
  • X-Linked Inhibitor of Apoptosis Protein / genetics*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism
  • Young Adult

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • BIRC5 protein, human
  • Benzamides
  • Inhibitor of Apoptosis Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Survivin
  • X-Linked Inhibitor of Apoptosis Protein
  • Imatinib Mesylate