Abstract

Efficacy of chemotherapy in treatment of canine metastatic mammary gland tumor (MGT) has not been well established yet. However, many studies had documented COX-2 inhibitor used alone has shown antitumor activity in canine MGT recently. The purpose of present report is to evaluate the pharmacological and tumoricidal effect of the combination of COX-2 inhibitor with doxorubicin on established canine MGT cell lines and hypothesize the combination would have synergistic effect. To study the effect of different concentration of meloxicam (1, 2, 4, 10, 50, 100 and 200 μM), and doxorubicin (62.5, 125, 250, 500, 1000 and 2000 nM) on the proliferation of MGT cells, both groups are cultured for 72 hours. All concentrations of meloxicam and doxorubicin are combined to result in 42 different concentration combinations and incubated for 72 hours. Cell proliferation is assessed using a standard MTT assay. The IC50 of meloxicam and doxorubicin is 93.57μM and 343.94 nM, respectively. Exposure of tumor cells to IC50 combinations of meloxicam and doxorubicin reveal only sub-additive effect. The result of cell proliferation in the lower concentration of meloxicam group does not show inhibitive effect in CMT-1 cell line. The combination effect of lower concentration of meloxicam and any concentration of doxorubicin compared with the doxorubicin group do not reveal statistically significant effect in CMT-1 cell line. However, the result of cell proliferation in the higher concentration of meloxicam group shows statistically significant inhibitive effect in CMT-1 cell line, and the combination effect of higher concentration of meloxicam and any concentration of doxorubicin revealed statistically significant sub-additive effect with using doxorubicin alone.

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