Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1)

Eur J Pharmacol. 2002 Feb 15;437(1-2):9-17. doi: 10.1016/s0014-2999(02)01267-0.


The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP1) in a human airway epithelial cell line (Calu-1) and to further assess whether budesonide, a potent antiasthma corticosteroid, alters the expression and activity of MRP1 in these cells. Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 microM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 microM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. Thus, budesonide inhibits MRP1 expression and may be useful as a chemosensitizer in tumor chemotherapy.

MeSH terms

  • Blotting, Western
  • Bronchodilator Agents / pharmacology*
  • Budesonide / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Indomethacin / pharmacology
  • Lung / cytology
  • Lung / drug effects*
  • Lung / metabolism
  • Multidrug Resistance-Associated Proteins / drug effects*
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Probenecid / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Verapamil / pharmacology
  • Vincristine / pharmacology


  • Bronchodilator Agents
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Budesonide
  • Vincristine
  • Verapamil
  • Probenecid
  • Indomethacin