The effect of new anti-erbb2 therapies and retinoic acid in human breast cancer cell proliferation

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

Mendoza

Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2016

Sociedad de Biología de Cuyo

Breast cancer is classified in molecular subtypes according to the presence/absence of estrogen receptor,progesterone receptor and ErbB-2. Tumors overexpressing ErbB-2 are more aggressive and metastatic; hencepatients have a poor prognosis. Therefore, anti-ErbB2 strategies have been developed, for instance the monoclonalantibody Trastuzumab. Currently they are being used in clinic treatments. Despite this progress, not all patientsrespond to the treatment. Thus, it is necessary to develop new therapeutic approaches based on the combination ofdifferent existing drugs. Retinoids have been suggested in the adjuvant treatment of breast carcinoma because of theirability to inhibit cell growth. We propose 1) To evaluate the effect of different concentrations of trastuzumab andretinoic acid on cell proliferation. 2) To determine whether the combination of both drugs exerts a synergistic effecton the reduction of cell proliferation. We used SKBR-3 and BT-474 breast cancer cell lines. The MTT assay andimmunofluorescence were performed. We demonstrated that, seventy two hours treatments of SKBR-3 and BT-474cells with different doses of Trastuzumab (0.1-1-10-100 µg/ml) and retinoic acid (RA) (10-8- 10-7-10-6- 10-5 M) areeffective decreasing cell proliferation in a dose-dependent manner. Additionally, combination of both drugs(Trastuzumab 1-10-100 µg/ml and retinoic acid 10-6 M) yields a potentiating effect on cell proliferation reductionwhich was observed in SKBR-3 cells but not in BT-474 cells. In conclusion, the sensibility to anti-Erb2 therapiescould be even greater with RA coadministrationin ER-/ErbB-2+ tumors.