Effect on the tumor microenvironment of metronomic chemotherapy with Cyclophosphamide (CY) and Losartan (LOS) in a murine model of mammary adenocarcinoma

KAUFMAN, CINTIA DANIELA; GRILLO, MÓNICA CAROLINA; BAGLIONI, MARÍA VIRGINIA; DEL GIÚDICE ANTONELA; ROZADOS, VIVIANA ROSA; SCHAROVSKY, OLGA GRACIELA; RICO, MARÍA JOSE; MAINETTI, LEANDRO ERNESTO

Mar del Plata

Congreso; Reunión Anual de Biociencia 2019; 2019

Sociedad Argentina de Investigaciones Clínicas

Metronomics, refers to all anticancer treatment regimens combining metronomic chemotherapy (chronic, low dose, no extended rest periods drug administration) and drug repositioning (the use of drugs originally formulated to other indications that showed antitumor effect). CY (drug with cytotoxic action on proliferating cells) and LOS (angiotensin II receptor antagonist, used to treat hypertension) were used in a metronomics schedule. We have demonstrated that the administration of metronomic CY+LOS in the triple negative M-234p mammary adenocarcinoma tumor model, inhibited tumor growth, increasing the survival rate without toxicity. Our aim was to study the effect of MCT with CY+LOS in M-234p tumor microenvironment. Female BALB/c mice were challenged s.c. with M-234p (day 0) and on day 6 divided in 4 groups (n=6-10/group). GI: Control, with no further treatment; GII: Treated with CY 25mg/kg/day in the drinking water; GIII: Treated with LOS 200mg/kg/day in the drinking water; GIV: Treated as GII+GIII. Mice were weighted and tumor volume measured 3 times/week. When tumors were exponentially growing, they were excised and used for immunohistochemistry and flow cytometry. GII and GIV exhibited a decreased number of HIF1α+ cells vs GI (P