STUDY OF THE EFFECTS OF LEUKOTRIENE A4 HYDROLASE INHIBITION ON THE HEPATOCELLULAR CARCINOMA CELL LINE HUH7

FRATTINI MAGALÍ; CHARES LAURA G; CEBALLOS MANCINI, MARÍA PAULA; FERRETTI, ANABELLA, C; OVIEDO BUSTOS, LUCÍA; COMANZO, CARLA G; PALMA NICOLÁS FRANCISCO; VERA, MARINA C; QUIROGA, ARIEL DARÍO; ALVAREZ, MARÍA DEL L.

BUENOS AIRES

Congreso; Reunión Anual Sociedad Argentina de Fisiología; 2023

Sociedad Argentina de Fisiología

Introduction: Leukotriene B4 (LTB4) is a lipid mediator synthesized from the hydrolysis of the precursor LTA4 by the action of theenzyme leukotriene A4 hydrolase (LTA4H). Our group demonstrated that the LTB4 signaling pathway plays an important role incontrolled proliferation during liver regeneration after partial hepatectomy; thus, it is also likely for it to play a role inuncontrolled proliferation occurring in liver cancer. Indeed, an overproduction of LTB4 has been shown in other types of humancancers, leading to proliferation of cancer cells. Objectives: To analyze the effects on specific behavior associated withmalignancy of tumor liver cancer cells, upon inhibition of the enzyme LTA4H. Methods: Human hepatocellular carcinoma (HCC)Huh7 cells were treated with the LTA4H inhibitors bestatin (BST) and SC-57461A (SC) or left untreated (control, C). Studies in 2Dcultures (C, BST and SC groups): cell viability, migration, clonogenicity, invasion, flow cytometry and the expression of keyproteins for proliferation and apoptosis. Studies in 3D cultures (C and SC groups): viability, proliferation and migration.Results: After performing dose-response curves, the established working concentrations were: BST 200 μM, SC 265 μM (2D),and SC 600 μM (3D). Viability: BST -26,4%**; SC -25,0%*. Migration: BST -25%**; SC -25%**. Clonogenicity: BST -28%*; SC -34%**. Invasion: BST -25,7%*; SC -28,9%**. Proliferation markers: PCNA: BST -48% *; SC +95%; Cyclin D1: BST -30%*; SC -66%*,(results are expressed as %C; *p