CHEMOTHERAPEUTIC DRUGS INDUCE THE ACTIVATION OF PROTEINS ASSOCIATED WITH TUMORIGENESIS AND DRUG RESISTANCE IN LOWER-GRADE TUMOR CELLS

RÍOS MEDRANO, MAYRA A.; PRADA, JESICA G.; CASTILLO, ANA F.; MALOBERTI, PAULA M. ; PODESTÁ, ERNESTO J.; ORLANDO, ULISES D.

Congreso; LXV Reunión anual de la sociedad argentina de investigacion clínica; 2020

Acyl CoA synthetase 4 (ACSL4) is an enzyme participating in the metabolism of arachidonic acid. ATP-binding cassette (ABC) transporters are transmembrane proteins that translocate low molecular weight molecules through ATP hydrolysis.We have previously shown that ACSL4 is involved in resistance to chemotherapeutic agents by regulating the expression of transporters; thus, the objective of this work was to study the effect of chemotherapeutic agents on ACSL4 and resistance mechanisms. The experimental model consisted in the chemotherapeutic challenge of adrenal cancer NCI-H295R and breast cancer MCF-7 cells, two lines characterized by low aggressive phenotypes and low expression of the ACSL4, ABCG2 and ABCC4 proteins. We evaluated cell functionality using proliferation (BrdU) and viability (MTT) assays, and compound exclusion (efflux) using fluorescent Hoechst 33342. ACSL4 and ABC transporters were evaluated by western blot (WB). NCI-H295R cell treatment with doxorubicin (20 nM) and cisplatin (200 nM) increased the expression of ACSL4 (WB-p