Effects of NF-κB Expression and Its Inhibition on Canine Mammary Cancer Cell Lines in an Immunodeficient Mice Model

Abstract

Two canine mammary gland tumor (MGT) cell lines, CHMp-5b and -13a, were transplanted into nude mice, and their tumor development and metastatic potential were evaluated. In addition, NF-κB, Ki-67 and cyclin D1 expressions in the tumor masses were evaluated, and the relationship between these expressions and malignancy of the tumors developed in nude mice was investigated. Lower activation of NF-κB was positively correlated with a lower potential of metastasis and better prognosis in nude mice xenografted with CHMp-13a compared with CHMp-5b. Then, CHMp-5b cells were treated with BAY11-7082, an inhibitor of NF-κB, and the expressions of I-κBα, p-I-κBα, cyclin D1 and Bcl-2 in these cells were evaluated by Western blot analysis. In addition, BAY11-7082 at a dose of 6 mg/kg was administered intraperitoneally to nude mice xenografted with CHMp-5b, and relationships between tumor growth and lung and lymph node metastasis in nude mice and NF-κB, I-κBα and p-I-κBα expressions in tissues of these mice were evaluated. BAY11-7082 treatment induced decreased expressions of p-I-κBα, cyclin D1 and Bcl-2 in a dose- and time-dependent manner, suggesting that BAY inhibited NF-κB in this cell line. CHMp-5b-xenografted mice treated with BAY11-7082 showed a reduction in tumor growth and metastasis. Therefore, inhibition of the NF-κB signaling pathway may be a promising novel therapeutic approach for canine MGTs.