Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1).
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.
Bandi
Nagesh
N
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Kompella
Uday B
UB
D015153:Blotting, Western; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D001993:Bronchodilator Agents; D019819:Budesonide; D007213:Indomethacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011339:Probenecid; D012333:RNA, Messenger; D014700:Verapamil; D014750:Vincristine