ACSL4 and COX-2 efects on cell aggressiveness and resistance to drugs in colon cancer cells

MARTINEZ, PONCE PALOMA; PRADA, JESICA G.; QUEVEDO, LUCIANO; BIGI, MARIA M.; CASTILLO, ANA FERNANDA; MALOBERTI, PAULA M.; ORLANDO, ULISES D.

Mar del Plata

Congreso; Congreso; Reunión anual de Sociedades de Biociencias. LXVIII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023; 2023

Tumor aggressiveness and drug resistance are major challenges for research in advanced colorectal cancer (CRC). Arachidonic acid (AA) metabolism plays an important role in colon carcinogenesis. Acyl-CoA synthetase 4 (ACSL4), an enzyme involved in AA metabolism, is upregulated in the transition from colon adenoma to adenocarcinoma. In other tumors, ACSL4 has been associated with resistance to treatment. AA is a substrate of cyclooxygenase-2 (COX-2), which is the isoform mainly involved in the pathogenesis of malignancy in CRC. Given that bioinformatic analyses have shown a significant increase in ACSL4 and COX-2 in patient samples of primary tumors, our aim was to relate ACSL4 and COX-2 expression to cell aggressiveness and drug resistance in different colon cancer cell lines. To this aim, we used SW48, SW480, Caco2, and HT29 cells, which differ in phenotype aggressiveness and drug resistance. We evaluated ACSL4 and COX-2 expression by western blot, and cell functionality through cell viability, proliferation, and clonogenicity assays. HT29 and SW480 cells had higher ACSL4 expression than SW48 and Caco2