Firocoxib as a Potential Neoadjuvant Treatment in Canine Patients with Triple-Negative Mammary Gland Tumors

Abstract

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.

Keywords

• cyclooxygenase-2
• caspase-3
• chemotherapy
• nonsteroidal anti-inflammatory drug