Efect of the combined treatment of Metformin (MET) and Propranolol (PROP) on different phases of tumor progression

BAGLIONI MV; ANSELMINO, LUCIANO E.; CESATTI LALUCE, NAHUEL; MAINETTI LEANDRO E; ROZADOS VIVIANA R; SCHAROVSKY OG; MENACHO-MÁRQUEZ MAURICIO; RICO MARÍA J

Congreso; Reunión Conjunta SAIC-SAI-SAFIS 2018; 2018

Drug repositioning refers to the use of drugs for different indications from the original ones. Met is an antidiabetic drug; Prop is a β-blocker. We found, in a triple negative breast cancer (TNBC) model, that Met+Prop treatment induced apoptosis, reduced proliferation and lung metastases. We aimed to test the effect of primary or adjuvant treatment with Met+Prop in intravasation, extravasation and lung colonization processes of 4T1 cells. We quantified the number of circulating epithelial cells (CEC:EpCAM+,CD34-,CD45-) in mice bearing 4T1 tumors in exponential growth, treated with Met(2g/l)+Prop(25mg/l) in the drinking water. The percentage of CECs in Met+Prop group was lower than in controls (P=0.066). To study the effect of Met+Prop in post-intravasation steps, BALB/c mice were i.v challenged with 5x104/100µl 4T1 cells labeled with green cell tracker proceeding as follows: G1) untreated mice injected with control cells; G2) untreated mice injected with in vitro pretreated cells [Met(5mM)+Prop(5µM)]; G3) mice receiving Met+Prop [Met(2g/l)+Prop(25mg/l)] injected with control cells. After two days, blood was collected and lungs excised. Mice in G2 and G3 showed lower percentage of circulating green cells (flow cytometry) than those in G1 (P