INSULIN-LIKE GROWTH FACTOR 2 MRNABINDING PROTEIN 1 (IGF2BP1) INVOLVEMENT IN ABC TRANSPORTERS MODULATION BY PHYTOESTROGENS IN HEPATOCARCINOMA CELL LINES

GOLA, ALDANA MAGALÍ; BUCCI-MUÑOZ, MARÍA; LIVORE VERONICA; MOTTINO, ALDO DOMINGO; CEBALLOS MARÍA PAULA; RUIZ MARÍA LAURA

Congreso; Reunion anual de Biociencias; 2022

P-glycoprotein (P-gp/ABCB1) and multidrug resistance associatedprotein 2 (MRP2/ABCC2) are canalicular export pumps thatextrude endo- and xenobiotics out of cells. Previously we reportedthat genistein (GNT, 1 and 10 μM) induces ABCB1 and ABCC2 inHepG2 cells. It was also demonstrated a link between these transportersand IGF2BP1. However, it has never been tested whetherother phytoestrogens like Dadzein (D) or S-Equol (E) modulate ABCtransporters in HepG2 cells and whether IGF2BP1 can mediate theregulation of ABC transporters by phytoestrogens. Aim: To evaluatethe effect of GNT, D and E on ABCB1, ABCC2 and IGF2BP1 proteinexpression and the role of IGF2BP1 in ABCB1 and ABCC2 regulationby phytoestrogens. Methods: HepG2 cells were incubated withGNT, D or E (0.1; 1; 10 μM) or vehicle (DMSO) for 48h. As culturemedium DMEM/F-12 phenol red free supplemented with charcoaldextran treated fetal bovine serum was used. IGF2BP1, ABCB1 andABCC2 protein levels were quantified by western blotting. IGF2BP1was transiently knocked down with a siRNA targeting human IGF2BP1mRNA (siRNA) or scrambled (SCR) as control. Cells weretreated, 24h after transfection, with GNT 1μM for 48h. The efficiencyof IGF2BP1 knock down was evaluated by western blotting. Results:All results are presented as mean±SEM, n=3, *p