PERSONAL DE APOYO
RÍOS MEDRANO Mayra Agustina
congresos y reuniones científicas
Título:
CHEMOTHERAPEUTIC DRUGS INDUCE THE ACTIVATION OF PROTEINS ASSOCIATED WITH TUMOROGENESIS AND DRUG RESISTANCE IN LOWER-GRADE TUMOR CELLS
Autor/es:
RIOS MEDRANO, MAYRA AGUSTINA; PRADA, JESICA G.; CASTILLO, ANA FERNANDA; MALOBERTI, PAULA M.; ERNESTO JORGE PODESTA; ORLANDO, ULISES D.
Lugar:
Caba
Reunión:
Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020, LXV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2020
Institución organizadora:
SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)
Resumen:
Acyl CoA synthetase 4 (ACSL4) is an enzyme participating in the metabolism ofarachidonic acid. ATP-binding cassette (ABC) transporters are transmembrane proteins thattranslocate low molecular weight molecules through ATP hydrolysis.We have previouslyshown that ACSL4 is involved in resistance to chemotherapeutic agents by regulating theexpression of transporters; thus, the objective of this work was to study the effect ofchemotherapeutic agents on ACSL4 and resistance mechanisms. The experimental modelconsisted in the chemotherapeutic challenge of adrenal cancer NCI-H295R and breastcancer MCF-7 cells, two lines characterized by low aggressive phenotypes and lowexpression of the ACSL4, ABCG2 and ABCC4 proteins. We evaluated cell functionalityusing proliferation (BrdU) and viability (MTT) assays, and compound exclusion (efflux)using fluorescent Hoechst 33342. ACSL4 and ABC transporters were evaluated by westernblot. NCI-H295R cell treatment with doxorubicin (20 nM) and cisplatin (200 nM) increasedthe expression of ACSL4 (WB-p <0.001), ABCG2 (WB-p <0.001) and ABCC4 (WB-p<0.05). The treatments also improved fluorescent compound exclusion (efflux-p <0.01), aneffect reversed by the action of ABGC2 transporter inhibitor KO143. Combined treatments(chemotherapeutic agents and ACSL4 inhibitor) reduced the proliferation of NCI-H295Rcells (BrdU-p <0.05). MCF-7 cell treatment with doxorubicin and cisplatin increased theexpression of ACSL4 (WB-p <0.001) and ABCG2 (WB-p <0.05) and the phosphorylationof pAKT (WB-p <0.05) and pS6 (WB-p <0.01), components of the AKT/mTOR pathway.These results are in line with our previous observation that ACSL4 regulates ABGC2expression through the regulation of the AKT/mTOR pathway. Therefore, ACSL4 mayconstitute a therapeutic target at the initial stages of chemotherapeutic treatment to preventthe activation of pathways associated with increased tumor aggressiveness.