Evaluation of COX-2 expression and antitumor effect of piroxicam and firocoxib on tumorspheres of canine prosthetic carcinomas and canine mammary carcinomas

Abstract

Mammary neoplasias are the most common type of tumor in female dogs with a mean age of 10 years. In male dogs, prostate neoplasias are uncommon, reaching only 0.6% of them. However, when a dog is diagnosed with prostatic carcinoma, the prognosis is unfavorable and usually evolves with the death of the patient due to the disease. In the human population, mammary carcinomas and prostatic neoplasias are the most incidental type of cancer in Brazil and the world. And the dog is considered a natural model for studying these two diseases in man. The origin of cancer in men and animals is still much discussed, and it is believed that cancer stem cells (CSC) are responsible for the initiation and spreading of tumors. In different carcinomas, COX-2 expression correlates with the presence of cancer stem cells, which overexpress this gene during its process of propagation and differentiation. Due to the ability of CSC to evade traditional therapeutic protocols (chemotherapy and radiotherapy), the present study aims to evaluate the expression of COX-2 in tumorspheres and the antiproliferative and pro-apoptotic effect of the in vitro treatment with Firocoxib and Piroxicam. Due to the importance of the dog as a model in comparative oncology, we propose to carry out the tests on culture samples of canine tumors and lines of human tumors. We will perform a cell sorting to isolate tumor stem cells, isolating cells that show CD44, OCT3 / 4 and ALDH1 positive marking and negative labeling for CD24. After separation of the cells with positive CSC markers, we will perform a tumorspheres assay to confirm the stem cell phenotype of the isolated population and also treat the cells with the mentioned drugs. (AU)