STUDY OF THE EFFECT OF GLYCEROL (GLY) ON THE SURVIVAL AND MIGRATION OF HEPATOCELLULAR CARCINOMA CELLS TREATED WITH SORAFENIB (SFB)

CHARES, LG; CARMELI BARBERIS, E; PALMA, NF; LIVORE, VI; FRATTINI, M; FERRETTI, AC; COMANZO, CG; OVIEDO BUSTOS, L; QUIROGA, AD; ALVAREZ, ML; CEBALLOS, MP

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SFB is used as a first-line therapy for HCC; however, its efficacyis limited and better therapies to prolong survival are still lacking.Combination therapy represents a major research direction for HCCtreatment. Our group reported antiproliferative and proapoptotic effectsof GLY administration in an in vivo model of liver carcinogenesis.Aim: to analyze whether GLY enhances the sensitivity of HCCcells to SFB in vitro. Methods: 2D and 3D cultures from Huh7 cellswere treated for 72 h with different concentrations of SFB or GLY toobtain dose-response curves. Alternative, cell cultures were treatedfor 72 h with SFB (2D: 2μΜ; 3D: 4μΜ), GLY (2D: 1μΜ; 3D: 2μΜ),SFB+GLY, or DMSO (control group). Then, cell viability (2D: MTT;3D: acid phosphatase; IC50), proliferation (3D: spheroid growth -volume 72h/0h) and migration (2D: wound healing; 3D: spheroidmigration) were assayed. Results: SFB and GLY reduced 2D and3D cell cultures viability in a dose-dependent manner compared withcontrol group. The 3D cell culture was less sensitive to drugs thanthe 2D cell culture (IC50: SFB 2D: 3.4μΜ, 3D: 13.7μΜ$; GLY 2D:2.4μΜ, 3D: 10μΜ$). In 3D cell cultures, both drugs induced dose-dependentgrowth inhibition. Cell cultures treated with SFB+GLYshowed a greater decrease in viability compared to cultures treatedwith SFB or GLY (2D: SFB -23%*, GLY -22%*, SFB+GLY -56%*#&;3D: SFB -16%, GLY -1%, SFB+GLY -42%*#&). Treatment of 3D cellcultures with SFB+GLY decreased spheroid growth compared to individualtreatments (SFB -25%*, GLY -11%*, SFB+GLY -35%*#&).SFB+GLY treatment produced the greatest reduction in cellular migrationin 2D and 3D cultures. $p<0.05 vs 2D; *p<0.05 vs control;#p<0.05 vs SFB; &p<0.05 vs GLY. Conclusions: GLY exacerbatedthe effects of SFB on HCC cellular survival and migration. Additionalstudies are needed to confirm the relevance of adding GLY duringSFB treatment and to elucidate the mechanisms involved.