Effect of the combined treatment with mifepristone and chemotherapy on breast cancer Brian metastases?

VERÓNICA DE LA FUENTE; OSVALDO PODHAJCER; AYELEN RUBIN; EDGARDO SALVATIERRA; PAOLA ROJAS; SILVIA VANZULLI; CLAUDIA LANARI

Mar del Plata

Congreso; Congreso de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE; 2016

EFFECT OF THE COMBINED TREATMENT WITH MIFEPRISTONE AND CHEMOTHERAPY ON BREAST CANCER BRAIN METASTASES The treatment of brain metastasis is limited due to the drug?s adversity to cross the blood brain barrier, because of the presence of endothelial cells? multidrug resistance efflux transporters, such as the P-glycoprotein (P-gp). The antiprogestin Mifepristone (MFP) is known to inhibit the P-gp activity. We hypothesize that a combination of MFP and Pegylated doxorubicin liposomes (doxo) improves the drug efficacy on tumors that do not express progesterone receptors. Using the metastatic triple negative MDA-231-BrM2 breast cancer cell line, transfected with GFP and luciferase, we explored different protocols to generate tumors growing in the brain of NSG mice. Spontaneous metastases were obtained by subcutaneous injection (sc) of 2 x 106 cells, and experimental metastases by intracardiac injection (ic) of 1 x 106 cells or by intracranial injection of 2 x 105 cells. In the ic and sc models small and scattered brain metastases as well as liver, lung and kidney metastases were observed. The intracranial model enabled us to obtain measurable brain tumors in a short time. Thus we selected this method to evaluate the effect of MFP (6 mg pellets, sc) and /or doxo (4,5 mg/kg, iv) on tumors growing in the brain. Treatment was initiated 10 days after cell inoculation. The amount of tumor cells after brain excision was measured by flow cytometry (GFP+ cells) and by luminometry (amount of luciferase). A decreased luminiscencesignal was observed in brains from mice treated with both agents as compared with the control mice (p