METFORMIN (M) AND PROPRANOLOL (P) ACT ON DIFFERENT STEPS of the metastatic cascade of a triple negative murine mammary adenocarcinoma

BAGLIONI, MARÍA VIRGINIA; ANSELMINO, LUCIANO; NAHUEL CESATTI LALUCE; LEANDRO E MAINETTI; VIVIANA R. ROZADOS; GRACIELA O. SCHAROVSKY; MENACHO MÁRQUEZ, MAURICIO; MARÍA JOSÉ RICO

Mar del Plata

Congreso; Reunión Anual SAIC-SAFE-SAB-SAP 2019; 2019

Drug repositioning refers to the application of drugs designed for other uses that showed an antitumor effect. Metformin is an antidiabetic drug, and propranolol is a β-blocker. We have found that M+P treatment reduced tumor volume and lung metastases number in a triple negative breast cancer (TNBC) model. Also, M+P combination showed a potential adjuvant effect in an in vivo experiment. Our aim was to deep our studies about metastatic cascade to corroborate our preliminary results in TNBC model (4T1) in BALB/c mice. We extracted blood from mice bearing tumors in exponential growth of Control (C) and M+P [treated with M(2g/l)+P(25mg/l)] groups (N). A lower epithelial cells (EpCAM+CD34-CD45-) percentage was found in M+P group (P=0.066). To characterize survival and extravasation of circulating tumor cells, mice were i.v inoculated with 5x104/100μl cells labeled with green cell tracker and divided as follows: C and M+P groups. After 2 days, M+P group showed lower percentage of circulating green cells (flow cytometry) (P