Antineoplastic effect of the cyclooxygenase inhibitor meloxicam on canine osteosarcoma cells

• Published in: Research in veterinary science 2006-06, Vol.80 (3), p.308-316
• Main Authors: Wolfesberger, Birgitt, Walter, Ingrid, Hoelzl, Claudia, Thalhammer, Johann G., Egerbacher, Monika
• Format: Article
• Language: English
• Subjects: Animals; antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; assays; biochemical pathways; Blotting, Western - veterinary; bone diseases; Bone Neoplasms - drug therapy; Bone Neoplasms - pathology; Bone Neoplasms - veterinary; Canine osteosarcoma; Caspase 3; Caspases - metabolism; Cell culture; Cell Line, Tumor; cell lines; cell proliferation; Cell Proliferation - drug effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase inhibitor; dog diseases; Dog Diseases - drug therapy; Dog Diseases - pathology; Dogs; dose response; drug evaluation; Immunohistochemistry - veterinary; in vitro studies; Life sciences; Meloxicam; messenger RNA; Microscopy, Electron, Transmission - veterinary; Microscopy, Fluorescence - veterinary; nonsteroidal anti-inflammatory agents; osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - pathology; Osteosarcoma - veterinary; pharmacokinetics; prostaglandin synthase; protein synthesis inhibitors; reaction inhibition; Reverse Transcriptase Polymerase Chain Reaction - veterinary; RNA, Neoplasm - chemistry; RNA, Neoplasm - genetics; Rodents; Studies; Thiazines - pharmacology; Thiazoles - pharmacology; Tumors; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2005.07.013

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.