Introduction

BMI-1 is an oncogene known to play a role in cell invasion, metastasis and chemoresistance. Previous studies have shown that Inhibition of BMI1 by the small molecule PTC-209 effectively suppresses proliferation of canine osteosarcoma cell lines. NSAIDs, such as piroxicam, are often prescribed when treating canine carcinomas and oral melanoma. The aim of this study was to evaluate the role of PTC 209 treatment alone or in combination with piroxicam on proliferation and survival of canine mammary carcinoma and melanoma cells.

Methods

Two canine mammary carcinoma cell lines (CMT12 and CMT27) and three melanoma cell lines (MM3, MM4 and MM5) were treated with PTC-209 or piroxicam alone and in combination. Differences in cell proliferation were assessed using an MTS assay and Western blots were used to evaluate alterations in BMI1 and AKT pathways.

Results

All five canine cell lines expressed BMI1. When treated with PTC-209, all cell lines showed a concentration dependent decrease in cell proliferation. Although statistically significant differences in IC50 values were observed, the CMT cell lines showed more resistance to PTC-209 treatment compared to the MM cell lines. Combination therapy significantly reduced proliferation of CMT and MM cell lines when compared to either drug treatment alone.

Conclusion

BMI1 may represent a novel target for treatment of canine melanoma and mammary carcinoma. Concurrent treatment with piroxicam may enhance targeted therapy against BMI1.