# Celecoxib Inhibits Vasculogenic Mimicry and Induces Apoptosis in the D17 Canine Osteosarcoma Cell Line via the COX-2/PGE2 Signaling Axis

## TL;DR

Celecoxib, an anti-inflammatory drug, may slow canine osteosarcoma growth by blocking blood-like channels and cell survival.

## Contribution

Celecoxib's inhibition of vasculogenic mimicry and apoptosis in canine osteosarcoma cells via COX-2/PGE2 is newly demonstrated.

## Key findings

- Celecoxib reduced D17 cell proliferation and induced apoptosis.
- Celecoxib disrupted vasculogenic mimicry formation on Matrigel.
- Celecoxib's effects were mediated through COX-2 and PGE2 reduction.

## Abstract

Osteosarcoma is an aggressive bone cancer in dogs that often spreads and shortens life expectancy. Tumors can form their own blood-carrying channels, a process called vasculogenic mimicry, which helps them grow and resist treatment. In this laboratory study, we tested celecoxib, a commonly used anti-inflammatory drug, on canine osteosarcoma cells to see whether it could reduce cancer cell survival and block formation of these channels. We found that celecoxib decreased cancer cell growth, increased programmed cell death, and prevented the cells from making blood-like channels. It worked by blocking a specific protein (COX-2) and reducing the production of a molecule (PGE2) that helps the tumor grow. These results suggest celecoxib may have potential as an additional treatment to slow tumor growth and reduce spread in dogs, but further studies in animals are needed to confirm safety and effectiveness before clinical use.

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.