Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma

J Cell Mol Med. 2023 Aug;27(15):2183-2193. doi: 10.1111/jcmm.17717. Epub 2023 Jun 19.

Abstract

Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.

Keywords: cyclooxygenase-2; feline injection-site sarcoma; primary cells; robenacoxib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carcinogenesis
  • Cats
  • Cell Transformation, Neoplastic
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Inflammation / complications
  • Sarcoma* / pathology
  • Soft Tissue Neoplasms* / etiology
  • Soft Tissue Neoplasms* / pathology
  • Soft Tissue Neoplasms* / veterinary
  • Tumor Microenvironment

Substances

  • Cyclooxygenase 2 Inhibitors
  • robenacoxib
  • Cyclooxygenase 2
  • Anti-Inflammatory Agents, Non-Steroidal