Abstract: This study was conducted to investigate the effect of enhancer of Zeste homolog 2 (EZH2) inhibitor GSK126 on the proliferation, migration, apoptosis and epithelial-mesenchymal transition (EMT) of canine mammary tumor cells. Canine mammary tumor cells (CHMm cells) in logarithmic growth phase were collected, and different concentrations of GSK126 (0, 10, 20, 40 μmol·L^-1) were used to culture CHMm cells. After 48 h, tetramethylazolium salt colorimetric method (MTT) and cell clone formation assay were detected for the proliferation ability of cells. Transwell assay was performed to evaluate the migration ability. The cell apoptosis was detected by Annexin V-FITC/PI flow cytometry, and the relative expression of apoptosis-related factors Bcl-2 and Bax, epithelial-mesenchymal markers E-cadherin, N-cadherin, Vimentin, EZH2 were determined by qRT-PCR and Western blot method. After treated with GSK126 for 48 h, the proliferation and migration of CHMm cells were inhibited in a concentration-dependent manner. The apoptosis rate of the GSK126 treatment group was significantly increased. The relative expression of pro-apoptotic factor Bax, epithelial marker E-cadherin mRNA and protein compared with control group was significantly increased as the concentration of GSK126 treatment group, in contrast, anti-apoptotic factor Bcl-2, mesenchymal marker N-cadherin, Vimentin and EZH2 mRNA and protein was significantly reduced. EZH2 inhibitor GSK126 may inhibit the proliferation, migration, EMT and induce apoptosis of canine mammary tumor cells, which provides a theoretical basis for the treatment of canine mammary tumor cells.

Key words: GSK126, canine mammary tumor, cell proliferation, apoptosis, epithelial-mesenchymal transition