Expression and function of renal drug transporters
upon cetuximab
pretreatment. Cells were pretreated with cetuximab (CTX) before gene
and protein expression was determined. The activity of renal drug
transporter was evaluated using fluorescent substrates (OAT1, fluorescein;
BCRP, Hoechst33342; P-gp, calcein and MRP4; GS-MF, respectively).
Changes in transport activity are depicted in fluorescent intensity
expressed in arbitrary units (a.u). CTX effectively reduced the expression
and activity of OAT1 (A, B) and BCRP (C, D), while increasing the
expression and activity of P-gp (E, F) and MRP4 (G, H). Protein expression
was determined for OAT1 (60 kDa) and BCRP (72 kDa) (A, C lower panel),
Na,K-ATPase was used as loading control (112 kDa). Data are presented
as mean values ± SEM, n = 3. Statistical analysis
was performed via unpaired Student’s t test.
∗, p < 0.05 and ∗∗∗, p < 0.01 compared to control (+EGF condition).