Metformin toxicity and effect on tumor growth in CBi mice challenged with M-406 mammary adenocarcinoma

MC CAPELLO GARDENAL, JM CÁCERES, L PAGURA, LE MAINETTI, MJ RICO, ROZADOS VR, SCHAROVSKY OG.

Rosario,Santa Fe

Congreso; XIII Congreso y XXXI Reunión Anual de la Sociedad de Biología de Rosario; 2011

Metformin is a biguanide used as an oral diabetes medicine. Recently, its inhibitory effect on tumor growth has been informed. Our aim was to explore the likeliness of metformin use in the metronomic treatment of M-406, evaluating its toxicity and effect on the tumor. Inbred CBi mice were challenged s.c. with M-406 (Day 0) and when the tumors reached @ 100mm3 volume were distributed in three groups: G (Group) I: Control, no further treatment; GII: received metformin in the drinking water (0,2 mg/ml) and GIII: ídem GII with metformin (0,4mg/ml). Tumor volume, body weight and metformin mean daily intake/animal were determined 2 times/week until mice euthanasia. Glycemia was determined on days 7, 14, 21. Tumor growth curves were adjusted to the exponential model Vt=S.e(k*t), [Vt=tumor volume (mm3) in time=t (days); S=time of latency constant; k=exponential growth rate] and tumor duplication time was calculated (TDup=0,69/k). No differences in TDup were observed between groups (GI: 3,15 days, GII: 3,63, GIII:3,52; median). No changes were observed within and between groups in glycemia, body weight and survival. Metformin chronic administration, in the studied doses, would not produce side effects and its antitumoral effect could be evaluated in combination with other drugs administered with a metronomic schedule.