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Chinese Journal of Oncology ; (12): 503-506, 2006.
Article in Chinese | WPRIM | ID: wpr-236948

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the anti-tumor effect and the mechanism of down-regulation of HER - 2 by cabamazepine in SKBR - 3 cells , a breast cancer cell line with HER - 2 over - expression.</p><p><b>METHODS</b>Western blotting was performed to evaluate the Her-2 expression level. The mRNA level of HER-2 was detected by RT-PCR. Immunoprecipitation was applied to detect the chaperon function and acetylation level of HSP90. The viability of cells was tested by MTT assay.</p><p><b>RESULTS</b>Cabamazepine treatment down-regulated HER-2 expression. Only HER-2 protein level decrease was observed with 10 micromol/L cabamazepine treatment, but both protein and mRNA expressions were inhibited by 100 micromol/L cabamazepine. Cabamazepine treatment could induce a higher acetylation level of HSP90 and destroy its chaperon function. Cabamazepine exerted synergism with Herceptin in promoting HER-2 protein degradation and synergism or potentiation with Herceptin or 17-AAG in inhibition of proliferation.</p><p><b>CONCLUSION</b>Cabamazepine can reduce the expression of HER-2 and show a synergistic effect with Herceptin or 17-AAG. There may be potential benefits of carbamazepine for cancer therapy in future. HER-2;</p>


Subject(s)
Female , Humans , Acetylation , Antibodies, Monoclonal , Pharmacology , Antibodies, Monoclonal, Humanized , Antineoplastic Agents , Pharmacology , Benzoquinones , Pharmacology , Blotting, Western , Breast Neoplasms , Metabolism , Pathology , Carbamazepine , Pharmacology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Drug Synergism , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins , Genetics , Metabolism , Histone Deacetylase Inhibitors , Lactams, Macrocyclic , Pharmacology , RNA, Messenger , Genetics , Metabolism , Receptor, ErbB-2 , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Trastuzumab
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