Celecoxib Inhibits Vasculogenic Mimicry and Induces Apoptosis in the D17 Canine Osteosarcoma Cell Line via the...

Osteosarcoma is a highly aggressive canine bone tumor characterized by early metastasis and resistance to chemotherapy. Vasculogenic mimicry (VM), the ability of tumor cells to form microvascular channels independent of endothelial cells, can contribute to tumor progression and poor prognosis. In this in vitro study, we evaluated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the canine osteosarcoma cell line D17. Celecoxib treatment significantly inhibited cell proliferation in a dose- and time-dependent manner, induced S-phase cell cycle arrest, and promoted apoptosis. Furthermore, celecoxib effectively disrupted VM formation on Matrigel. Transcriptome analysis revealed that celecoxib downregulated genes associated with angiogenesis and the COX pathway, notably PTGS2. Consistent with this, celecoxib treatment reduced the secretion of prostaglandin E2 (PGE2) in a dose-dependent manner. Crucially, the addition of exogenous PGE2 restored VM formation in celecoxib-treated cells, confirming that celecoxib-mediated VM suppression is dependent on the reduction of PGE2 levels. These findings establish the COX-2/PGE2 signaling axis as a key regulator of VM in D17 canine osteosarcoma cells and that celecoxib warrants further preclinical evaluation as a strategy to target both tumor growth and alternative vascularization.