The combined treatment of ATRA and Lapatinib induces cytotoxic effects and modulates retinoid genes expression on cancer stem cell component of triple-negative breast cancer cell line

DIEGO BRITEZ NEIRA; ANDRES BECHIS; LIZETH ARIZA BAREÑO; LUCIANA CAÑONERO; ALDANA SCHEY; ALEJANDRO J. URTREGER; LAURA B. TODARO

Mar del Plata

Congreso; LXVIII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Sociedad Argentina de Investigación Clínica (SAIC)

Cancer stem cells (CSCs) are resistant to both chemotherapy and radiotherapy and are considered the seed of metastasis. In order to validate a new therapeutic strategy against this component, throughout the current study, we examined the effect of the combined treatment of All-Trans Retinoic Acid (ATRA) and Lapatinib on several parameters related to CSCs and metastatic dissemination in human triple-negative mammary tumor cell lines (HS578T and 4T1). The Lapatinib treatment dose for both cell lines was previously determined as 5µM for HS578T and 1µM for 4T1 which correspond to their respective IC50 values.A decreased clonogenic capacity was observed in the combined treatment for both cell lines. However, in HS578T cells, a significant decrease was observed upon Lapatinib treatment alone. Furthermore, a decrease in cell adhesion and an increase in EGFR expression were evident in HS578T cells under the combined treatment.Regarding CSCs, on monolayers treated over 48hs less compact spheres with a clustered appearance could have been observed for both Lapatinib and the combined treatment, accompanied by a significant decrease in diameter and an increase in the number of spheres. The qPCR analysis of retinoid system genes revealed a significant increase in RARγ (nuclear retinoic receptor involved in stemness) in both ATRA and combination treatment.The cytotoxic effects on cell monolayers observed in previous studies, with the effects evidenced on CSCs of Lapatinib, either alone or in combination with ATRA in both triple-negative breast cancer models, provide further in vitro evidence of the potential repositioning of these drugs for the treatment of HER2-negative breast cancer.