The in vitro effects of piroxicam and meloxicam on canine cell lines.
OBJECTIVE
To analyse the direct antiproliferative effects of both piroxicam and meloxicam at a variety of concentrations on a series of canine cancer cell lines and the mechanism of cell death.


METHODS
The in vitro effects of piroxicam and meloxicam at various concentrations on canine cell cultures (Madin-Darby canine kidney cells, osteosarcoma, mammary carcinoma, and lymphoma) were assessed with respect to proliferation inhibition and apoptosis induction. Western blot analysis of cyclooxygenase-1 and cyclooxygenase-2 expression was performed on all cell lines.


RESULTS
All cell lines used in this study were cyclooxygenase-1 and cyclooxygenase-2 positive apart from Madin-Darby canine kidney cells which were negative for both cyclooxygenase-1 and cyclooxygenase-2. Both meloxicam and piroxicam were able to inhibit proliferation in cell lines in a dose-dependent manner. However, the drug concentration required for a given effect was cell line dependent.


CONCLUSIONS
The results suggest that significant inhibition of proliferation and induction of apoptosis would only occur when drug concentrations were in excess of those that can be achieved in vivo following maximum recommended dose rates. It is possible, however, that local or topical treatment or altered dosing regimens may offer alternative approaches to the use of these drugs as antineoplastic agents.
Knottenbelt
C
C
Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH.
Chambers
G
G
Gault
E
E
Argyle
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western / Q000662:veterinary; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000032:analysis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D000077239:Meloxicam; D012516:Osteosarcoma / Q000188:drug therapy / Q000662:veterinary; D010894:Piroxicam / Q000494:pharmacology* / Q000627:therapeutic use; D013843:Thiazines / Q000494:pharmacology* / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000077239:Meloxicam