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

CHARES LAURA G; CARMELI BARBERIS E; PALMA NICOLÁS FRANCISCO; LIVORE, VERÓNICA INÉS; FRATTINI M; FERRETTI, ANABELA C; COMANZO, CARLA G; OVIEDO BUSTOS L; QUIROGA, ARIEL D; ALVAREZ, MARÍA DE L.; CEBALLOS, MARÍA PAULA

Congreso; LXVII Reunión Científica Anual de SAIC; 2022

SFB is used as a first-line therapy for HCC; however, its efficacy is limited and better therapies to prolong survival are still lacking. Combination therapy represents a major research direction for HCC treatment. Our group reported antiproliferative and proapoptotic effects of GLY administration in an in vivo model of liver carcinogenesis. Aim: to analyze whether GLY enhances the sensitivity of HCC cells to SFB in vitro. Methods: 2D and 3D cultures from Huh7 cells were treated for 72 h with different concentrations of SFB or GLY to obtain dose-response curves. Alternative, cell cultures were treated for 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: spheroid migration) were assayed. Results: SFB and GLY reduced 2D and 3D cell cultures viability in a dose-dependent manner compared with control group. The 3D cell culture was less sensitive to drugs than the 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-dependent growth inhibition. Cell cultures treated with SFB+GLY showed a greater decrease in viability compared to cultures treated with SFB or GLY (2D: SFB -23%*, GLY -22%*, SFB+GLY -56%*#&; 3D: SFB -16%, GLY -1%, SFB+GLY -42%*#&). Treatment of 3D cell cultures with SFB+GLY decreased spheroid growth compared to individual treatments (SFB -25%*, GLY -11%*, SFB+GLY -35%*#&). SFB+GLY treatment produced the greatest reduction in cellular migration in 2D and 3D cultures. $p