Involvement of the glycan-binding protein galectin-1 in hepatocellular carcinoma cell drug resistance.

BACIGALUPO, MARÍA L.; ELOLA, MARÍA TERESA; WOLFENSTEIN-TODEL, CARLOTA; ESPELT, MARÍA V.; RUBIN, AYELEN; LANARI, C.; ROJAS, P.; TRONCOSO, MARÍA F.; CARABIAS, PABLO; SAFFIOTTI, NICOLÁS; ROSSI, J.P.; RABINOVICH, GABRIEL A.

PRAGA

Congreso; European Association for the Study of the Liver (EASL) Liver Cancer Summit 2020; 2020

European Association for the Study of the Liver (EASL)

Involvement of the glycan-binding protein galectin-1 in hepatocellular carcinoma cell drug resistance Carabias P1, Bacigalupo ML1,2, Rubin A3, Saffioti N1,2, Elola MT1,2, Lanari C3, Rossi JP1,2, Wolfenstein C1,2, Rojas P3, Rabinovich GA3,4, Espelt MV1,2, Troncoso MF1,21 Universidad de Buenos Aires (UBA). Facultad de Farmacia y Bioquímica. Departamento de Química Biológica. Buenos Aires, Argentina.2 Consejo Nacional de lnvestigaciones Científicas y Técnicas (CONICET). Instituto de Química y Fisicoquímica Biológicas (IQUIFIB). Buenos Aires, Argentina.3 Consejo Nacional de lnvestigaciones Científicas y Técnicas (CONICET). Instituto de Biología y Medicina Experimental (IByME). Buenos Aires, Argentina 4 Universidad de Buenos Aires (UBA). Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Buenos Aires, Argentina.Background and Aims: Hepatocellular carcinoma (HCC) is characterized by a high resistance to chemotherapy. P-glycoprotein (Pgp) is an ATP-dependent drug efflux pump and its overexpression in HCC is associated with a decrease in intracellular drug concentration, leading to chemotherapeutic tolerance. Galectin-1 (Gal1), a β-galactoside-binding protein, is overexpressed in HCC and it is related to tumor aggressiveness. Recent studies suggest that Gal1 may have a role in HCC chemoresistance. Our aim was to investigate the molecular basis of Gal1-mediated chemoresistance in HCC cells.Methods: We stably transfected human HCC HepG2 cells to overexpress (HepG2Gal1) or silence (shRNA) Gal1 expression, with the corresponding control transfections. To investigate Gal1 involvement in HCC chemoresistance in vivo, we evaluated whether HepG2Gal1 cells could generate doxorubicin (DOX)-resistant tumors in immunodeficient NSG mice. MTT assay was performed to determine if different levels of Gal1 expression affect viability in cells exposed to DOX or sorafenib. To elucidate the involved mechanism, the amount of intracellular DOX was determined using fluorescence techniques. The effect of Gal1 on Pgp expression was studied by immunoblotting.Results: We observed a decrease in the volume of control-derived tumors treated with DOX (4.5 mg/kg i.v. once a week, 3 weeks) compared with HepG2Gal1-derived treated tumors (0.43±0.03cm3 vs 1.39±0.38cm3, p