Low-Dose Cyclophosphamide and Piroxicam Inhibit Growth, Migration, and Invasion of Canine Oral Malignant Melanoma Cell Line

Abstract

The effect of low-dose chemotherapy on tumor motility of canine oral malignant melanoma has been investigated on an in vitro model using low-dose cyclophosphamide and piroxicam. Cyclophosphamide, at a concentration of 0.1 mg/mL in culture medium, significantly inhibited tumor cell migration/invasion through trans-well assays and suppressed both ERK and NF-κB signaling, the latter of which was observed through IκB-α and P-IκBα expression. Furthermore, in combination with a COX-2 inhibitor, i.e. piroxicam (0.38 mg/mL in culture medium), cyclophosphamide revealed a potential anti-migration effect over the single piroxicam treatment on a wound assay. This result suggested that low-dose cyclophosphamide might have influence on tumor cell motility by inhibition of the NF-κB/ERK cascade.