Fig. 2.

SPA70 antagonizes hPXR target genes induced by various hPXR agonists. a CYP3A4 protein levels in primary human hepatocytes treated with vehicle control (0.1% DMSO), 1 μM rifampicin (RIF), 0.1 μM SR12813 (SR) or 0.03 μM T090137 (T0) in the presence or absence of 2.5 μM SPA70 for 48 h. Primary human hepatocytes from at least three donors were used; representative data from donor #HH1811-1 are shown. b MDR1 protein levels in LS180 and LS174T cells treated for 72 h with 1.6 μM RIF and 10 μM SPA70 alone or in combination (RIF + SPA70: simultaneous co-treatment; RIF + SPA70 pretreatment: cells treated with SPA70 24 h before RIF treatment). Final DMSO concentration was 0.2% in both a, b. The levels of β-actin were used as loading controls. The numbers between the blots indicate the relative intensity of the protein bands (CYP3A4 or MDR1) in the respective lanes, with the DMSO-treated sample being set as 1.0. c DNA microarray analysis (with representative results displayed as a heatmap), showing the expression of hPXR transcriptional target genes in human hepatocytes in response to hPXR agonists (RIF, SR or T0) with or without SPA70 co-treatment