Arsenic trioxide and triptolide synergistically induce apoptosis in the SKM-1 human myelodysplastic syndrome cell line

Although certain combination therapies comprising arsenic trioxide (As(2)O(3)) with other agents exist for the treatment of several types of human cancer, few As(2)O(3) combination therapies are clinically effective for myelodysplastic syndromes (MDS). Triptolide (TL) may be an effective therapeutic agent for the treatment of MDS. However, to date, there is no combination therapy for MDS with As(2)O(3) and TL. Therefore, the aim of the present study was to investigate this combination therapy on the apoptosis of MDS SKM-1 cells. The MDS SKM-1 cells were treated with As(2)O(3), TL or the two in combination at various concentrations, or were mock-treated. Cell viability, cell apoptosis, levels of reactive oxygen species (ROS) and the expression of the cell apoptosis-associated genes, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3, were determined using an MTT assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide double-stained cells, flow cytometic analysis of intracellular 2′,7′-dichlorodihydrofluorescein diacetate fluorescence and reverse transcription-quantitative polymerase chain reaction analysis, respectively. Combination index (CI) analysis was performed to determine whether effects were synergistic (CI<1). The combination treatment was found to synergistically inhibit MDS SKM-1 cell growth, induce cell apoptosis, increase ROS levels, upregulate the expression levels of Bax and caspase-3, and downregulate the mRNA expression of Bcl-2. In conclusion, the combination treatment of As(2)O(3) and TL synergistically induced apoptosis in the MDS SKM-1 cells.