In vitro effects of meloxicam with or without doxorubicin on canine osteosarcoma cells

Cyclooxygenase ( COX) inhibitors, already widely used to reduce fever, inflammation and pain, are under increasing consideration as potential agents for the prevention and treatment of neoplasia. As COX-2 was detected in human and canine osteosarcomas, we have evaluated the effect of the preferential COX-2 inhibitor meloxicam on an established D-17 canine osteosarcoma cell line, which expressed, as well as COX-1 and COX-2 also COX-3 ( as demonstrated by Western blot). An XTT proliferation kit was used to assess surviving cells after drug treatment. At low concentrations ( 1, 2, 4 and 10 mu M) meloxicam caused an increase in cell numbers while a marked antiproliferative effect was observed at higher concentrations ( 100, 200 mu M) after 3 days and also 3 weeks of incubation. The chemotherapeutic drug doxorubicin showed a cytotoxic effect at all concentrations ( 60 - 1920 nM). Exposure of tumour cells to combinations of meloxicam and doxorubicin revealed synergistic effects ( with 240 nM doxorubicin), as well as sub-additive and antagonistic results, especially if combined with concentrations of meloxicam typically found in serum. Care should be taken in concluding, on the basis of one in vitro study, that meloxicam does not have a role in the treatment of canine osteosarcomas given that the results from in vivo studies may differ.