Reduced expression of HSP27 following HAD-B treatment is associated with Her2 downregulation in NIH:OVCAR-3 human ovarian cancer cells

The Korean traditional medicine, HangAmDan (HAD), was developed in 1996 for use as an antitumor agent, and has since been modified to HAD-B (an altered form of HAD), in order to potentiate its therapeutic effects. In the present study, the effect of HAD-B on the proliferation and invasion of NIH:OVCAR-3 and SKOV-3 human ovarian cancer cell lines was investigated. In addition, the expression of major signal transduction molecules and changes in the proteome in these cells were measured. HAD-B treatment effectively induced a reduction in the levels of cell proliferation in serum-free conditioned media. However, unaltered levels of PARP and caspase-3 indicated that HAD-B does not reduce proliferation by inducing apoptotic cell death. Fluorescence-activated cell sorting analysis revealed no significant change in apoptosis following HAD-B treatment. Invasion assay results indicated a reduced rate of invasion following HAD-B treatment. HAD-B also influenced the expression of major signal transduction molecules; the phosphorylation of mTOR and AKT was reduced, while that of ERK was increased. Alterations in the proteomes of the two cell lines were investigated following HAD-B treatment. Among the 9 proteins with differential expression, heat-shock protein β-1 (HSP27) was downregulated in NIH:OVCAR-3 cells treated with HAD-B. The reduced expression of HSP27 was associated with human epidermal growth factor receptor 2 (Her2) downregulation in these cells. In conclusion, the results of the current proteome assessment suggest that HAD-B has the potential to suppress the proliferation and invasion of human ovarian cancer cells. HAD-B treatment of NIH:OVCAR-3 cells suppressed HSP27 expression and was also associated with Her2 downregulation.