Abstract: Objective To investigate the effect of sodium valproate, a histone deacetylase inhibitor, on the cytotoxicity of
doxorubicin in breast cancer cells. Methods Western blotting was used to assess Cx43 protein expression in breast cancer
Hs578T cells exposed to doxorubicin and sodium valproate. MTT assay was used to determine the cytotoxicity of doxorubicin;
annexin V/PI double staining and Hochest 33258 fluorescence staining were employed to detect doxorubicin-induced early
and late apoptosis, respectively. Results Western blotting showed that sodium valproate significantly increased Cx43 protein
expression in Hs578T cells (P<0.01). The cells exposed to both sodium valproate and doxorubicin showed significantly lowered
cell viability compared with the cells exposed to doxorubicin alone (P<0.01). Exposure to both sodium valproate and
doxorubicin resulted in significantly increased early and late cell apoptosis rate compared with doxorubicin treatment alone
(P<0.01). Conclusion sodium valproate can significantly enhance the cytotoxicity of doxorubicin and increase
doxorubicin-induced apoptosis in breast cancer cells in vitro possibly by enhancing the gap junction function.