To evaluate the effect of different doses,forms and compatibility of selenium on canine breast cancer cells CTM1211and to explore the related mechanisms,CTM1211 cells were intervened by different doses of CTX(cyclophosphamide:1,2,4 mg/mL),SSE(selenite:10,20,40 μmol/L),MSA(methylseleninic acid:10,20,40 μmol/L),MSC(selenocysteine:200,400,800 μmol/L),CTX+SSE(0.5 mg/mL+5 μmol/L,1 mg/mL+10 μmol/L,2 mg/mL+20 μmol/L),CTX+MSA(0.5 mg/mL+5 μmol/L,1 mg/mL+10 μmol/L,2 mg/mL+20 μmol/L) and CTX+MSC(0.5 mg/mL+100 μmol/L,1 mg/mL+200 μmol/L,2 mg/mL+400 μmol/L) for 24 h,48 h and 72 h,and the cell viability of each group was determined by MTT.While simplified cells were intervened by CTX(2 mg/mL),SSE(40 μmol/L),MSA(20 μmol/L),MSC (400 μmol/L) and CTX+MSA(2 mg/mL+20 μmol/L) for 48 h and the cell apoptosis rate was measured by flow cytometry,the protein and mRNA expression of VEGF-a(vascular endothelial growth factor a),PTEN(phosphatase and tensin homolog),Ang-2(angiopoietin-2) and HIF-1a(hypoxia inducible factor 1a) were measured by immunohistochemistry and RT-qPCR,respectively.The cell viability of each group at 48 h/72 h was significantly lower(P<0.01 or P<0.05),while the apoptosis ratewas significantly higher at each time point (P<0.01) than that of the control group,and the effect of group CTX + MSA was the most significant.Generally,the expression of VEGF-a,Ang-2 and HIF-1a protein and mRNA were significantly low,while that of PTEN were significantly up regulated.In conclusion,selenium,especially MSA,could significantly inhibit breast cancer cell CTM1211,which is partly due to the induction of apoptosis and regulation of tumor angiogenesis-related factors VEGF-a,PTEN,Ang-2 and HIF-1a by selenium.