부산대학교 도서관

Simple Summary: Mammary gland tumors are most frequent in non-castrated female dogs and represent an interesting model for understanding tumor biology of human breast cancer. Ciclooxigenase-2 (COX-2) is an enzyme associated with the inflammatory process and different studies have implied the association of COX-2 expression with patient's prognosis. However, few studies have investigated the effects of drugs that block COX-2 enzyme. In this context, we performed in vitro and in vivo experiments to understand the effect of COX-2 blockers on mammary cancer cells that overexpress COX-2. We found an induction of mammary cancer cell apoptosis after treatment with COX-2 inhibitors indicating the role of COX-2 enzyme in mammary cancer cell maintenance. Moreover, COX-2 inhibitors can represent therapeutic effects on triple-negative mammary cancer. This study aimed to investigate the pro-apoptotic effects of NSAID (Previcox®) in vitro and in vivo. Two CMT cell lines, one from the primary tumor and one from bone metastasis, were treated with firocoxib and MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) value. The firocoxib IC50 for the cell lines UNESP-CM5 and UNESP-MM1 were 25.21 µM and 27.41 µM, respectively. The cell lines were then treated with the respective firocoxib IC50 concentrations and annexin V/propidium iodide (PI) assay was performed, to detect the induction of apoptosis in both cells (Annexin+/PI+). We conducted an in vivo study involving female dogs affected by CMT and divided them into control and treatment groups. For both groups, a biopsy was performed on day 0 (D0) and a mastectomy was performed on day 14 (D14). In the treatment group, after biopsy on D0, the patients received Previcox® 5 mg/kg PO once a day until mastectomy was performed on D14. COX-2/caspase-3 double immunostaining was performed on samples from D0 and D14, revealing no difference in the control group. In contrast, in the treatment group Previcox® increased the number of COX-2 positive apoptotic cells. Therefore, firocoxib can induce apoptosis in CMT cells in vitro and in vivo, and Previcox® can be a potential neoadjuvant treatment for patients with mammary cancer. [ABSTRACT FROM AUTHOR]