Evaluation of the potential mechanisms responsible for intrinsic resistance to chemotherapy drugs and their possible association with the epithelial or mesenchymal phenotype in canine mammary carcinomas cells

Abstract

One of the limiting factors for success in the treatment of breast cancer is resistant to chemotherapy. Tumors may have intrinsic resistance, when there is no response even in the first cycle of treatment. Increased drug efflux, higher DNA damage and lower DNA repair caused by chemotherapy, are mechanisms related to the intrinsic resistance of a cell. It is evident that the resistance to chemotherapeutics is overcome, the number of survivors and the effectiveness of treatment would be highly significant. Therefore, will be evaluated in this project, mechanisms responsible for intrinsic resistance to chemotherapy drugs doxorubicin, cisplatin and paclitaxel, and analyze their association with their phenotypes and resistance in cells derived of canine mammary carcinomas. 4 lineage will be used strains of mammary carcinoma cells, which will be subjected to cytotoxicity testing, using MTT assay, to examine cell viability in relation to the chemotherapeutic doxorubicin, cisplatin and paclitaxel. It will be analyzed gene expression of ABCB1 using the Real-Time PCR. The induction of DNA damage will be performed using treatment with hydrogen peroxide, the damage and DNA repair will be analyzed from the comet assay. Therefore, knowledge of the intrinsic resistance mechanisms of canine breast carcinoma, it is extremely important to analyze a possible combination with efficient treatment of the cells with the chemotherapeutic doxorubicin, cisplatin and paclitaxel, so it becomes possible to amplify the efficiency of future chemotherapy treatments in the species. (AU)