Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4

Figure 5

Trans effect of dabrafenib mesylate on hOAT4-mediated transport in COS-7 cells. Cells expressing hOAT4 were preloaded (PL) with dabrafenib mesylate (Dab, 100 mM) or unlabeled hOAT4 substrate estrone sulfate (100 mM) for 1 h, followed by washing with PBS and a subsequent exposure (EXP) to PBS containing ³H-labeled estrone sulfate (300 nM). 4 min later, the uptake was stopped by rapidly washing the cells with ice-cold PBS. Intracellular accumulation of ³H-labeled estrone sulfate was then counted. Each data point represents only carrier-mediated transport after subtraction of values from parental cells and was expressed as a percentage of the uptake measured in cells without preloading with dabrafenib mesylate or positive control. The results shown are means ± SE (n = 3). p < 0.05.