IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SYNERGISTIC ANTITUMOR ACTIVITY AGAINST THE HER-2 POSITIVE HUMAN BREAST CANCERS CELLS BY COMBINING TRASTUZUMAB WITH RETINOIC ACID.
Autor/es:
FLAMINI MI; REDONDO AL; VARGAS ROIG LM; SÁNCHEZ AM; VANDERHOEVEN F
Lugar:
Merlo
Reunión:
Congreso; Sociedad de Biología de Cuyo; 2017
Resumen:
Breast cancer is classified in molecular subtypes. Tumors overexpressing HER-2 are more aggressive and metastatic; hence patients have a poor prognosis. Therefore, anti-HER-2strategies have been developed, for instance the monoclonal antibody Trastuzumab (Tz).Despite this progress, not all patients respond to the treatment. Retinoids¸ mainly retinoic acid (RA), have been suggested in the adjuvant treatment of breast carcinoma because of their ability to inhibit cell growth. Moesin and FAK are proteins involved in cell adhesion and migration. We propose to evaluate the effect of anti-HER-2 therapies in combination or not with RA on the viability, adhesion, migration, invasion and expression of moesin, FAK and HER-2 receptorin human breast cancer cells. We usedSKBR-3 and BT-474 breast cancer cell lines. The MTT assays, pharmacological interaction analysis, immunofluorescence, adhesion, migration and invasion assays, and western blot were performed.Thecoadministration of both drugssynergistically decreased cell proliferation. Simultaneous administration of the two drugs significantly decreased adhesion, migration and invasion in both cell lines. By immunofluorescence it was observed that Tz+RAinduced FAK translocation from the cytoplasm to the nucleus. In addition, a granular distribution of HER-2 receptor was observed after the combined treatments. RA and Tz combined treatments strongly decrease FAK, Moesin and HER-2 expression. In conclusion, the coadministration of both drugs in patients with this type of cancer could contribute to improve their prognosis and reduce the adverse effects of therapy because the Tz doses applied would be lower due to the adjuvant effect of RA.