Synergistic antiproliferative effect of the combination of 2’nitroflavone and gefitinib in triple negative breast cancer cells

JULIETA R CEBRÓN; MARIANA A BOJORGE; VIVIANA C BLANK; MARIEL MARDER; JOHANNA G MIQUET

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitorused for the treatment of cancer which has recently been proposedfor the treatment of certain types of breast cancer. 2’nitroflavone(2’NF) is a synthetic flavone that was obtained in our institute whichhas previously demonstrated to affect the EGFR pathway activationas well as the expression of receptors related to EGFR activity inbreast cancer cells. As EGFR is associated with tumorigenesis andis believed to be involved in the mechanism of action of flavonoids,a combinatory therapy between 2’NF and gefitinib is proposed.The aim of our investigation is to analyze if there is a synergisticeffect that justifies the combination of these two molecules for thetreatment of breast cancer. To assess our objective, MDA-MB-231breast cancer cells were treated with 2’NF, gefitinib or a combinationof both for 48 h. The effect on cell proliferation was determined byhexosaminidase assay using concentrations in a range between 0.1μM and 150 μM. Afterwards, the synergistic effect was determinedusing Compusyn software that calculates a combinatory index (CI)which value must be under 1 to have a synergistic effect. Besides,the results were confirmed by flow cytometry using concentrationsof 5 μM and 10 μM. Results were analyzed by ANOVA, p