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Revista de investigación clínica

versión On-line ISSN 2564-8896versión impresa ISSN 0034-8376


GARCIA-QUIROZ, Janice et al. Astemizole, an Inhibitor of Ether-À-Go-Go-1 Potassium Channel, Increases the Activity of the Tyrosine Kinase Inhibitor Gefitinib in Breast Cancer Cells. Rev. invest. clín. [online]. 2019, vol.71, n.3, pp.186-194.  Epub 12-Abr-2021. ISSN 2564-8896.


Expression and activity of the potassium channel ether-à-go-go-1 (EAG1) are strongly related to carcinogenesis and tumor progression, which can be exploited for therapeutic purposes. EAG1 activity may be reduced by preventing its phosphorylation with epidermal growth factor receptor (EGFR) kinase inhibitors and by astemizole, which blocks the channel pore and downregulates its gene expression.


We aimed to study the potential cooperative antiproliferative effect of the EGFR inhibitor gefitinib and the EAG1-blocker astemizole, in breast cancer cells.

Materials and Methods

The cells were characterized by immunocytochemistry. Inhibitory concentrations were determined by non-linear regression analysis using dose-response curves. The nature of the pharmacological effect was evaluated by the combination index equation while cell cycle analysis was studied by flow cytometry.


Astemizole and gefitinib inhibited cell proliferation in a concentration-dependent manner, with inhibitory concentrations (IC 50) values of 1.72 µM and 0.51 µM, respectively. All combinations resulted in a synergistic antiproliferative effect. The combination of astemizole and gefitinib diminished the percentage of cells in G2/M and S phases, while increased accumulation in G0/G1 of the cell cycle.


Astemizole and gefitinib synergistically inhibited proliferation in breast cancer cells expressing both EGFR and EAG1. Our results suggest that the combined treatment increased cell death by targeting the oncogenic activity of EAG1.

Palabras llave : Breast cancer; Combination index; Epidermal growth factor receptor; Astemizole; Gefitinib.

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