COMBINED THERAPY WITH CHLOROQUINE AND PROPRANOLOL FOR COLORECTAL AND TRIPLE NEGATIVE BREAST CANCERS TREATMENT

LUCIANO ANSELMINO; MARÍA VIRGINIA BAGLIONI; GUSTAVO CHAPO; MAURICIO MENACHO MÁRQUEZ

Congreso; II Reunión Científica Internacional, VII Reunión Científica Regional, VI Congreso Nacional de Ciencia y Tecnología de Animales de Laboratorio; 2021

Drug repositioning refers to new uses for existing drugs outside the scope of their original medicalindications. This approach fastens the process of drug development allowing finding effective drugs withreduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, whenthe probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the mostaggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, availabletreatments are generally associated to severe side effects. In our work, we explored the effect of combiningchloroquine (CQ) and propranolol (Prop), two repositioned drugs, in both tumor types. We demonstrate byin vitro experiments that CQ+Prop treatment affects viability, apoptosis and migratory potential of CRC andTNBC cells. To corroborate our data in in vivo models, CRC and TNBC cells were subcutaneously injectedinto the right flank of 8-week-old female mice (BALB/c or immunodeficient mice according to the cell type;CICUAL authorization for the project “Nuevos enfoques terapéuticos para el tratamiento del cáncer”,Facultad de Ciencias Médicas, UNR). Animals were fed with commercial diet, water ad libitum, and kept in12h light/dark cycles at the CIPReB facilities. Tumor volume was periodically measured with a caliper. Whentumors reached 80 mm3 animals were arbitrarily separated and treated by adding CQ and/or Prop to the drinking water (65 and 7mg/kg/day respectively, N=4-6/group). Body weight and tumor growth wereperiodically monitored. When tumors reached the maximum size ethically allowed, animals were sacrificedby overexposure to CO2. Tumor, spleen and lungs were removed for histological analysis. The resultsindicated that CQ+Prop treated animals carrying CRC showed lower tumor growth kinetics than the controlgroup (P