Antineoplastic effect of the cyclooxygenase inhibitor meloxicam on canine osteosarcoma cells.
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.
Wolfesberger
Birgitt
B
Clinic of Internal Medicine and Infectious Diseases, University of Veterinary Medicine, Vienna, Austria.
Walter
Ingrid
I
Hoelzl
Claudia
C
Thalhammer
Johann G
JG
Egerbacher
Monika
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000662:veterinary; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D007150:Immunohistochemistry / Q000662:veterinary; D000077239:Meloxicam; D046529:Microscopy, Electron, Transmission / Q000662:veterinary; D008856:Microscopy, Fluorescence / Q000662:veterinary; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D012334:RNA, Neoplasm; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D053148:Caspase 3; D020169:Caspases; D000077239:Meloxicam