Objective  To investigate the mechanism of histone deacetylase (HDAC) inhibitor in down-regulating the expression of HER-2 in breast cancer cells and to provide an innovative therapeutic option to overcome the disadvantages of anti-HER-2 therapy.

  Methods  HER-2-positive breast cell lines were treated with HDAC inhibitors. The changes in the gene and protein levels of HER-2 were detected by qPCR and Western blot. MiRNA microarray was used to identify the HDAC inhibitors, whereas qPCR was used to verify the miRNA expression.

  Results  In vitro cell experiments confirmed that the HDAC inhibitors TSA and SAHA can down-regulate the expression of HER-2 in breast cancer cell lines. TSA can down-regulate the expression of HER-2 gene in BT474 and decrease the concentrations of 100 nmol by 10.7% and 200 nmol by 38.9% (P < 0.05). TSA had no effect on the primary cells. The expression of HER-2 gene of BT474 was down-regulated by 93.9% (P < 0.05) in the 5 μmol/L group but not in the 1 μmol/L group. SAHA significantly affected the primary cells at a concentration of 1 μmol/L and reduced the cells at 87.1% at a concentration of 5 μmol/L. Seven miRNAs were identified from the miRNA microarray. MiR-762 was used as a basis to identify the changes in miRNA. The miRNA sputum identified by miRNA microarray and qPCR may be associated with the down-regulation of HER-2 by HDAC inhibitors.

  Conclusion  HDAC inhibitors may down-regulate the expression of HER-2 in breast cancer cells by changing some miRNAs.