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

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

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor used for the treatment of cancer which has recently been proposed for the treatment of certain types of breast cancer. 2’nitroflavone (2’NF) is a synthetic flavone that was obtained in our institute which has previously demonstrated to affect the EGFR pathway activation as well as the expression of receptors related to EGFR activity in breast cancer cells. As EGFR is associated with tumorigenesis and is 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 synergistic effect that justifies the combination of these two molecules for the treatment of breast cancer.MDA-MB-231 breast cancer cells were treated with 2’NF, gefitinib or a combination of both for 48 h. The effect on cell proliferation was determined by hexosaminidase assay using concentrations in a range between 0.1 µM and 150 µM. Afterwards, the synergistic effect was determined using 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 concentrations of 5 µM and 10 µM. Results were analyzed by ANOVA, p