Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line

Trastuzumab has efficacy to improve the effect of cytotoxic drugs, such as paclitaxel and anthracyclin, against HER2-overexpressing breast cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, is known to have anti-tumoral properties. However, whether and how trastuzumab possesses the potential to synergize the anti-tumor effect of NaB on breast cancer cells is still equivocal. To elucidate whether combined treatment with NaB and trastuzumab exerts antitumor effects on a HER2-overexpressing breast cancer cell line, SKBR3 cells were treated with NaB alone or in combination with trastuzumab, and the effects on proliferation and cell cycle progression were analyzed. Combinatory treatment with NaB (4 mmol/l) and trastuzumab (20 mu g/ml) significantly increased the growth-inhibitory effect on SKBR3 breast cancer cells, in comparison to NaB or trastuzumab treatment alone. The growth-inhibitory effect of the combination of NaB and trastuzumab was accompanied by elevated mRNA and protein levels of the cyclin-dependent kinase inhibitor p27(Kipl). In contrast, this effect was absent in HER2-negative HCC1937 cells. In conclusion, trastuzumab significantly improved the antitumor effect of NaB on HER2-overexpressing breast cancer cell line in vitro.