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

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

Congreso; Sociedad de Biología de Cuyo.; 2016

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; hence patients have a poor prognosis. Therefore, anti-ErbB2 strategies have been developed, for instance the monoclonal antibody Trastuzumab. Currently they are being used in clinic treatments. Despite this progress, not all patients respond to the treatment. Thus, it is necessary to develop new therapeutic approaches based on the combination of different existing drugs. Retinoids have been suggested in the adjuvant treatment of breast carcinoma because of their ability to inhibit cell growth. We propose 1)To evaluate the effect of different concentrations of trastuzumab and retinoic acid on cell proliferation. 2) To determine whether the combination of both drugs exerts a synergistic effect on the reduction of cell proliferation. We used SKBR-3 and BT-474 breast cancer cell lines. The MTT assay and immunofluorescence were performed. We demonstrated that, seventy two hours treatments of SKBR-3 and BT-474 cells 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) are effective 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 reduction which was observed in SKBR-3 cells but not in BT-474 cells. In conclusion,the sensibility to anti-Erb2 therapies could be even greater with RA coadministrationin ER-/ErbB-2+ tumors.