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

CARABIAS P; BACIGALUPO ML; RUBIN A; SAFFIOTI N; ELOLA MT; LANARI C; ROSSI JP; WOLFENSTEIN C; ROJAS P; RABINOVICH GA; ESPELT MV; TRONCOSO MF

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)

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