Antineoplastic effect of the cyclooxygenase inhibitor meloxicam on canine osteosarcoma cells

Res Vet Sci. 2006 Jun;80(3):308-16. doi: 10.1016/j.rvsc.2005.07.013. Epub 2005 Sep 22.

Abstract

A decisive role in cancer development has been attributed to cyclooxygenase-2 (COX-2) activity, but the significance of COX-2 inhibitors in cancer treatment still needs to be thoroughly investigated. We studied the influence of meloxicam, a non-steroidal antiinflammatory drug with preferential inhibitory effects on COX-2 compared to COX-1, on canine osteosarcoma (D-17) cells. We demonstrated that D-17 cells expressed mRNA and COX-2 protein. Treatment with meloxicam induced a time- and dose-dependent inhibition of cellular growth. To determine if apoptosis plays a role in meloxicam-induced cell death, we performed agarose gel electrophoresis and found a DNA-ladder pattern, typically seen in apoptosis, as well as early apoptotic changes by Annexin V tests. Furthermore, electron microscopy revealed ultrastructural alterations typical of apoptosis. Quantification of apoptotic cells by immunohistochemical staining of caspase 3 confirmed the results. However, further studies with meloxicam are necessary to assess its potential use for treatment of osteosarcomas in dogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western / veterinary
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / veterinary*
  • Caspase 3
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dog Diseases / drug therapy*
  • Dog Diseases / pathology
  • Dogs
  • Immunohistochemistry / veterinary
  • Meloxicam
  • Microscopy, Electron, Transmission / veterinary
  • Microscopy, Fluorescence / veterinary
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Osteosarcoma / veterinary*
  • RNA, Neoplasm / chemistry
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / veterinary
  • Thiazines / pharmacology*
  • Thiazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • RNA, Neoplasm
  • Thiazines
  • Thiazoles
  • Cyclooxygenase 2
  • Caspase 3
  • Caspases
  • Meloxicam