OBJECTIVETo 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.

METHODSWestern 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.

RESULTSCabamazepine 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.

CONCLUSIONCabamazepine 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;