Synergistic antitumor activity against the HER-2 positive human breast cancers cells by combining trastuzumab with retinoic acid

VANDERHOEVEN F; REDONDO AL; VARGAS ROIG LM; SÁNCHEZ AM ; FLAMINI MI.

villa de merlo

Congreso; XXXV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2017

Sociedad de Biología de Cuyo

Breast cancer is classified in molecular subtypes. Tumors overexpressing HER-2 are moreaggressive and the patients have a poor prognosis. Therefore, the use of anti-HER-2 monoclonalantibody Trastuzumab (Tz) has been adopted. Unfortunately, some patients are unresponsive to thistherapy. Retinoids¸ mainly retinoic acid (RA), have been suggested as adjuvant treatment of breastcarcinoma because of their ability to inhibit cell growth. Moesin and FAK are proteins involved incell adhesion and migration. We propose to evaluate the effect of a combined therapy (anti-HER-2plus RA) on the viability, adhesion, migration, invasion and expression of moesin, FAK and HER2 receptor in human breast cancer cell lines SKBR-3 and BT-474. MTT assays, pharmacologicalinteraction analysis, immunofluorescence, adhesion, migration and invasion assays, and westernblot were performed. The coadministration of both drugs synergistically decreased cell proliferation.Moreover, simultaneous administration of the two drugs significantly decreased adhesion, migrationand invasion in both cell lines. By immunofluorescence, we determined that Tz+RA induced FAKtranslocation from the cytoplasm to the nucleus. In addition, a granular distribution of HER-2receptor was observed after the combined treatments. RA and Tz combined treatments stronglydecrease FAK, Moesin and HER-2 expression. In conclusion, the coadministration of both drugs inpatients with this type of cancer could contribute to improve their prognosis and reduce the adverseeffects of therapy because the Tz doses applied would be lower due to the adjuvant effect of RA.