Figure 5

Figure 5

Effects of dabrafenib on hPXR target genes expression in LS174T-hPXR cells and in primary human hepatocytes. (A) RT-qPCR of CYP34A, ABCG2 and FGF19 mRNA expression were performed in LS1747-hPXR cells treated with 3 μM SR12813 or dabrafenib for 24 h. Results were obtained from three independent experiments performed in duplicate. Data are expressed as mean ± sd and compared with control cells treated with DMSO (0.1%). (B) RT-qPCR of CYP34A and CYP2B6 mRNA expression in primary cultures of human hepatocytes (three independent donors: FT438, FH439 and FH440) following 48 h treatment with the indicated concentrations of ligand. The relative gene expression levels were normalized using GAPDH content for LS174T-hPXR cells and for RPLP0 for human hepatocytes. mRNA expressions are expressed as mean ± sd of three independent experiments and compared with DMSO-treated LS174T-hPXR cells or hepatocytes, **** p < 0.0001, *** p < 0.001, ** p < 0.01, * p < 0.1 (Student’s t-test).