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International Journal of Pharmacology
Year: 2005  |  Volume: 1  |  Issue: 1  |  Page No.: 85 - 92

Modulation of MDR1 Gene Expression by a Chronic Treatment with Verapamil in Caco-2 Cells

Marilena Granzotto, Cristina Zadro, Ilenia Drigo, Fiora Bartoli and Giuliana Decorti    

Abstract: The aim of this study was to investigate the effect of a chronic treatment with low doses of verapamil, as used in cardiovascular therapy, on the expression of mRNAs coding for transport proteins, in cultured Caco-2 cells. Caco-2 cells were selected in vitro through continuous exposure to stepwise increasing concentrations of verapamil. The Caco-2/ver cell line, a resistant sub line tolerating 50 μM verapamil, was obtained after a chronic treatment with this drug. Parental and resistant cells were grown for 20 days and then used for doxorubicin uptake and transport studies. The expression of P-gp and CYP3A4 mRNAs was examined by RT-PCR. Evaluation of doxorubicin uptake demonstrated a reduced drug accumulation in the resistant cell line compared to parental Caco-2 cells. Transport studies across cell monolayer showed an increased basal to apical transport rate in Caco-2/ver in comparison to Caco-2 cells. The relative expression of mRNA for MDR1 gene was greater in treated cells, whereas CYP3A mRNA levels were unaffected.

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