Activity of intestinal efflux pumps in m-406 mammary adenocarcinoma bearing mice with Metabolic Syndrome (MS) treated with cyclophosphamide (cy) Metronomic Chemotherapy (MC

BARRANCO, MARIA MANUELA; HABIB, MARTIN JOSE; DI CARLO, BIANCA; SIGAL, NICOLAS; SYLVESTRE BEGNIS, MARIA; ZECCHINATI, FELIPE; DEL GIUDICE, ANTONELA; RICO, MARIA JOSE; ROZADOS, VIVIANA; SCHAROVSKY O, GRACIELA; VILLANUEVA, SILVINA STELLA MARIS; GARCÍA, FABIANA; MAINETTI LEANDRO

MAR DE PLATA

Congreso; 2 REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

High fat diet (HFD) cause obesity and MS, which are associated with breast cancer progression. MC (chronic, low dose, with no extended rest periods, drug administration) is a promising treatment strategy with low toxicity. Some chemotherapeutic drugs are substrates of multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp), efflux pumps that limit the intestinal absorption and are modified by alterations produced in MS. We previously demonstrated the induction of MS in CBi male mice. The aim was to assess the alteration produced by MS in Mrp2 and P-gp activity as intestinal biochemistry barrier and its influence on the therapeutic effect of CY MC. CBi male mice (5 weeks n=20/group), were fed with a chow diet (C) and a diet with 40% calories of fat (HFD) throughout the experiment. At 16 weeks, the development of MS was confirmed by biochemical and morphological parameters. The activity of Mrp2 and P-gp was evaluated using the in vitro model of everted intestinal sacs. Once the MS features were settled, mice were challenged s.c. with M-406 (day 0); when the tumor was palpable, mice were distributed into 4 groups (n=8/group): GI: C no treatment, GII: C+Cy (30 mg/kg/day in drinking water), GIII: HFD no treatment and GIV: HFD+CY. Efflux of Mrp2 substrate DNP-SG decreased 64% in HFD respect to C (P