CHLOROQUINE: REPOSITIONING OF A MALARIA DRUG FOR COLORECTAL CANCER TREATMENT NEW DATA FROM A CHEMICALLY INDUCED INTESTINAL TUMORIGENESIS MODELS

INGRID SPESSOTTI; MARTINEZ MARIGNAC VERONICA; NATALIA ROMERO; ERNESTO RIDEL; MAURICIO MENACHO MARQUEZ

BUENOS AIRES

Encuentro; REUNION CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIC SAIB SAA SAFE SAFIS SAH SAP SAB SAI

Colorectal cancer (CRC) is the second leading cause ofcancer-related death in Argentina. The application of mousemodels or study of patient disease development is the goldstandard to the identification and pre-clinical validation ofnovel therapeutic targets in colorectal cancer as well for thesearch for early disease biomarkers. However, it have beensuggested that preclinical xenograf rodent-based tumormodels are not predictive of human clinical outcomes for thisreason we have established an animal tumor models that areinduced by exposure to chemical carcinogens (IEC models)like azoxymethane (AOM) and dextran sulfate sodium (DSS)treatment in mice that may offers a powerful model ratherxenograf models in the characterization of the initiation ofaberrant crypt foci (early lesions) and in the evaluation ofCRC chemopreventive strategies.This study was performed to investigate the anticancer effectand the tumor reverting capacity of Chloroquine on AOM/DSS induced CRC in Balb/c mice. We induced colorectal tumorsin male mice and evaluated the effects of Chloroquine treatment after week 11 of induction on tumor tissue morphology.By using histology, Haematoxylin and Eosin stainingand TEM, we confirmed the establishment of tumour andaberrant crypt foci ultra structure by week 10 and 20 from theinduction. The administration with Chloroquine from week 11significantly decreased the incidence of tumor formation andinflammation by week 30 (P