Inhibition of HSP90 by triptolide (TPL) augments Bortezomib-induced U266 cells apoptosis

Abstract

HSP90 has high expression in myeloma cells and very important for prognosis, and that triptolide (TPL), the main active component of the traditional Chinese herbal medicineTripterygium wilfordii Hook F (Celastraceae) has the inhibition effects in the growth of myeloma cells. In this study, we test the ability of TPL to induce apoptosis in U266 human myeloma cells by reducing HSP90 expression, as well as the effect of TPL on Bortezomib sensitivity. The MTT cell viability assay was used to assess growth inhibition of U266 human myeloma cells due to different TPL concentrations and the combined use of different concentration of TPL and 0.01 mM Bortezomib. Annexin-V and Propidium iodide (PI) labeling were used to detect cell death and determine the mode of death. TPL alone inhibited U266 cell growth and apoptosis inducement in a concentration-dependent manner. When TPL is combined with 0.01 mM Bortezomib, both effects increase. Western blotting revealed that caspase 3 and caspase 9 gene expression increased, while nuclear factor (NF)-KB and HSP 90 protein expression decreased, related with apoptosis and growth inhibition. TPL increases U266 cell sensitivity to Bortezomib, inducing apoptosis, which might be the result of suppress NF-KB and HSP90 activity. Key words: Bortezomib, multiple myeloma, heat shock protein gp90, triptolide.