Effects of NF-κB Expression and Its Inhibition on Canine Mammary Cancer Cell Lines Using an Immunodeficient Mice Model
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概要
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Two canine 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 on the tumor masses were evaluated and 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, when compared to CHMp-5b. Then, CHMp-5b were treated with BAY11-7082, an inhibitor of NF-κB and expression of I-κBα, p-I-κBα, cyclin D1 and Bcl-2 on these cells were evaluated on Western blot analysis. In addition, BAY11-7082 at a dose of 6 mg/kg was administrated 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 on 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 reduction in tumor growth and metastasis. Therefore, inhibition of the NF-κB signaling pathway may be a promising novel therapeutic approach for canine MGTs.
著者
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NISHIMURA Ryohei
Laboratory of Veterinary Emergency Medicine, Graduate School of Agricultural and Life Sciences, The
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MOCHIZUKI Manabu
Laboratory of Veterinary Diagnostic Imaging, Department of Veterinary Medicine, Tokyo University of
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Sasaki Nobuo
Laboratory Of Veterinary Surgery Faculty Of Agriculture University Of Tokyo
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Endo Yoshifumi
Laboratory Of Veterinary Surgery Graduate School Of Agricultural And Life Sciences University Of Tok
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Nakagawa Takayuki
Laboratory Of Developmental Immunology And Crest Program Of Japan Science And Technology Agency Grad
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MKAOUAR Lobna
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University
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