EFFECTS OF METFORMIN IN COMBINATION WITH 2-DEOXYGLUCOSE ON FELINE MAMMARY CARCINOMA CELLS

ARBE, MF; FONDELLO, C; AGNETTI, L; GLIKIN, GC; FINOCCHIARO, LME; VILLAVERDE, MS

Congreso; 51 Annual Meeting of Argentine Society for Biochemistry and Molecular Biology (SAIB); 2015

Most tumor cells metabolism rely in an exacerbation of glycolisys which increased the malignant phenotype. Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease. The aim of the present work was to investigate the in vitro effects of a combination of metformin (MET, antidiabetic drug, OXPHOS inhibitor) and 2-deoxyglucose (2DG, hexokinase inhibitor) on two cell lines, AlRB (HER2 positive) and AlRATN (HER2 negative) derived from a spontaneous feline mammary carcinoma. AlRB and AlRATN were grown as both monolayers (M) and spheroids (S). After 24 h of culture, cells were treated with 0.5 mM 2DG, 1 mM MET or a combination of both MET-2DG. Concentration-response curve were also assessed. The antitumor effects of bioenergetic inhibition were evaluated by the acidic phosphatase assay (APH), 5 days (M) or 9 days (S) after treatments. We found that both cells lines significantly decreased cell viability in a concentration dependent manner after 2DG or MET treatments. AlRB were more sensitive to 2DG than AlRATN when cultured as monolayers (p menor a 0.05). On the contrary, AlRATN where more sensitive to MET than AlRB when culture as spheroids and also compared with its respective monolayers. Finally, the combination of MET-2DG potentiated the individual effects only in AlRB monolayers. The results reported here support further studies to investigate the potential use of this metabolic modulation approach in a clinical setting.