Antiproliferative effects of oxytocin and desmopressin on canine mammary cancer cells

Abstract

Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient?s overall survival. Several in vitro studies performed on murine and human cancer cells have suggested that some peptide hormones can modulate tumor growth. However, little is known about its effects on canine cancer. The aim of the present study was to evaluate the effects of Oxytocin (OT) and Desmopressin (DDAVP) on proliferation of the canine mammary cancer cell line CMT-U27. The cells were grown in 96-well plates, at two densities (4x103 and 8x103 cells/well) in 200 µl of RPMI-1640 supplemented with 10% Fetal Bovine Serum. After overnight culture, the medium was removed and replaced with medium containing OT or DDAVP at five concentrations: 10, 50, 100, 500 and 1000 nM, or medium without drugs (controls). After 72 h of incubation, cell viability was determined using the MTT colorimetric dye reduction method. With 4x103 cells/well, OT at 1000 nM resulted in a 25% of inhibition of cell viability (p<0.01). Surprisingly, OT 50 nM resulted in a higher inhibitory effect (18%) than 500 nM (9%). At 8x103 cells/well, OT showed a significant antiproliferative effect (almost 25%) with the highest concentration (p<0.05). Desmopressin at 1000 nM and 4x103 cells/well reduced cell growth by 22% (p<0.05). At 50, 100, 500 nM the inhibitory effect was lower. With 8x103cells/well, DDAVP at 100, 500 and 1000 nM exhibited a mild antiproliferative effect (p>0.05). In conclusion, OT and DDAVP can inhibit proliferation of CMT-U27 cells, by almost 20% at the highest concentrations. Further studies are required to evaluate its potential as antitumor agents, alone or combined with conventional cytotoxic drugs, for the treatment of dogs with advanced mammary cancer.