TUMOR MICROENVIRONMENT: EFFECT OF METRONOMIC CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE (CY) AND LOSARTAN (LOS) ON M-406 MURINE MAMMARY ADENOCARCINOMA

GRILLO, MÓNICA CAROLINA; KAUFMAN, CINTIA DANIELA; 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

Metronomic chemotherapy (MCT) refers to the chronic, equally spaced, delivery of low doses of chemotherapeutic drugs, without extended interruptions. Drug repositioning (DR) in oncology refers to the use of drugs originally formulated for other indications that showed antitumor potential. CY is an alkylating drug with toxic action on proliferating cells. LOS is an antagonist of angiotensin II receptor, used to treat hypertension. Tumor microenvironment is constituted by genetically stable cells that surround and feed the tumor, favoring sustained growth, invasion and metastasis. It was previously shown that MCT with CY+LOS inhibited M-406 growth and increased mice survival without general toxic effects. Our objective was to study the effect of metronomic CY+LOS treatment, on M-406 tumor microenvironment. CBi female mice were challenged s.c. with M-406 (day 0) and distributed on day 6, into 4 groups (n=6-7/group). GI: Control, non-treated; GII: Treated with CY 25mg/kg/day in the drinking water; GIII: Treated with LOS 50mg/kg/day in the drinking water; GIV: Treated as GII+GIII. Mice weight and tumor volume were determined 3 times/week. When tumors reached the exponential growth phase, mice were euthanized, tumors excised and prepared for immunohistochemical analysis. Foxp3+ cells/field decreased significantly in GIV compared to GI (P