Antiestrogen is one type of the endocrine therapeutic agents for estrogen 
receptor α (ERα)-positive breast cancer. Unfortunately, this treatment alone is 
insufficient. Here we reported a novel potential anticancer strategy by using 
histone deacetylase (HDAC) inhibitor to enhance the action of endocrine therapy 
in ERα-positive breast cancer cell. The well-described HDAC inhibitor, 
trichostatin A (TSA), and antiestrogen raloxifene were found to, respectively, 
inhibit E2-induced proliferation of MCF-7 breast cancer cell in a 
dose-responsive and time-dependent manner. TSA and raloxifene enhanced the 
antiproliferative activity of each other by promoting cell death via apoptosis 
and cell cycle arrest. Thus, they displayed better antiproliferative effects in 
combined treatment than that with either agent alone. The expression level of 
estrogen receptor β (ERβ) showed a marked increase after TSA or/and raloxifene 
treatment. Treatments with TSA or/and raloxifene resulting in the up-regulation 
of ERβ are in accordance with the antiproliferative effects of the two agents. 
Furthermore, the over-expression of ERβ by adenovirus delivery could inhibit the 
proliferation of MCF-7 tumor cells and drastically enhanced the 
antiproliferative effects of TSA and raloxifene. These results demonstrated that 
the interference of ERβ on the antiproliferative effects of HDAC inhibitor and 
antiestrogen constitutes a promising approach for breast cancer treatment.