Anti-Tumour Effects of Paclitaxel on Canine Osteosarcoma and Melanoma Cell Lines

Abstract

In dogs, solid tumours are one of the most life-threatening diseases, including mammary gland tumours, mast cell tumours, squamous cell carcinoma, osteosarcoma, and malignant melanoma. Paclitaxel, a chemotherapeutic agent from the taxane family, is used for the treatment of human and canine solid tumours. A new oral formulation of paclitaxel (Liporaxel® Sol.) has been developed, but its anti-tumour effects on malignant canine tumour are unknown. The purpose of this study was to determine the anti-tumour effects of paclitaxel on canine osteosarcoma and melanoma cell lines and to assess the clinical safety of oral paclitaxel in normal dogs. The anti-tumour effects of paclitaxel on D17 (canine osteosarcoma cells) and LMeC (canine melanoma cells) were detected by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay, cell cycle analysis, and annexin-V assay. To evaluate the safety of oral paclitaxel, three healthy dogs were orally administered 5 mg/kg paclitaxel every 7 or 14 days for 8 weeks. Complete blood counts and serum chemistry analyses were performed and the data were compared by one-way analysis of variance. Paclitaxel significantly inhibited the proliferation of D17 and LMeC cells. The flow cytometric analysis revealed that the cell cycles in both malignant cell lines were arrested in the G2/M phase and that paclitaxel induced cell apoptosis. The healthy dogs that received oral paclitaxel for 8 weeks did not exhibit any clinical signs and all blood parameters were within the normal ranges. In conclusion, oral paclitaxel might be a viable, novel chemotherapeutic agent for malignant canine tumours, particularly osteosarcoma and melanoma.