Arsenic trioxide and triptolide synergistically induce apoptosis in the SKM‑1 human myelodysplastic syndrome cell line.
Although certain combination therapies comprising arsenic trioxide (As2O3) with other agents exist for the treatment of several types of human cancer, few As2O3 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 As2O3 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 As2O3, 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 As2O3 and TL synergistically induced apoptosis in the MDS SKM‑1 cells.
Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Hai-Ying
HY
Hua
Department of Hematology, The Third Affiliated Hospital of Nantong University, Wuxi, Jiangsu 214041, P.R. China.
Hua-Qiang
HQ
Gao
Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Ai-Ning
AN
Sun
Laboratory of Cell and Molecular Biology, Jiangsu Institute of Hematology, Suzhou, Jiangsu 215006, P.R. China.
Jian-Nong
JN
Cen
Laboratory of Cell and Molecular Biology, Jiangsu Institute of Hematology, Suzhou, Jiangsu 215006, P.R. China.
Li-Li
LL
Wu
D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage*; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D010087:Oxides / Q000008:administration & dosage*; D010616:Phenanthrenes / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D001152:Arsenicals; D004224:Diterpenes; D004852:Epoxy Compounds; D010087:Oxides; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C001899:triptolide; D053148:Caspase 3; D000077237:Arsenic Trioxide
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