Fig. 4.

Effect of tyrosine kinase inhibitors (TKIs) on the membrane protein abundance of hepatic bile acid transporters in sandwich-cultured human hepatocytes (SCHH). SCHH were treated with 0.1% DMSO control (Ctrl), dasatinib (1.8 μM), pazopanib (6.6 μM) or sorafenib (4.3 μM) for 24 hours. Abundance of bile salt export pump (BSEP), sodium taurocholate co-transporting polypeptide (NTCP), epidermal growth factor receptor (EGFR), and Na⁺/K⁺ ATPase (loading control) was evaluated using immunostaining of membrane fractions harvested from SCHH lots EGO, RVQ, and WID. Densitometry was performed using ImageJ and BSEP, NTCP, and EGFR signals were normalized to Na⁺/K⁺ ATPase. All treatments were performed in triplicate except in lot WID (n = 2). Statistically significant differences in lots EGO and RVQ were assessed using repeated measures two-way ANOVA with Dunnett’s multiple comparison test (*, P < 0.05, **, P < 0.0001, TKI versus control).