蟾毒灵通过下调 survivin 的表达诱导急性早幼粒细胞白血病细胞凋亡。
Bufalin induces the apoptosis of acute promyelocytic leukemia cells via the downregulation of survivin expression.
机构信息
Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, PR China.
出版信息
Acta Haematol. 2012;128(3):144-50. doi: 10.1159/000339424. Epub 2012 Aug 10.
BACKGROUND AND AIMS
Bufalin is a cardiotonic steroid isolated from the Chinese toad venom preparation Chan'su and has been shown to induce leukemia cell differentiation and apoptosis under certain experimental conditions. However, the detailed mechanism by which bufalin induces the apoptosis of acute promyelocytic leukemia cells is largely unexplored.
METHODS
The acute promyelocytic leukemia cell line NB4 was treated with bufalin, then the proliferation was evaluated by cell viability assay and apoptosis was detected by flow cytometry analysis. In addition, NB4 cells were treated by MEK inhibitor PD98059 in combination with bufalin, and the expression of survivin and activation of caspase-3 were detected by Western blot analysis.
RESULTS
Bufalin inhibited the proliferation and induced the apoptosis of NB4 cells in a dose- and time-dependent manner. Moreover, bufalin synergized with PD98059 to inhibit the proliferation and induce the apoptosis of NB4 cells, which was associated with the downregulation of survivin expression and the upregulation of caspase-3 activation.
CONCLUSIONS
Bufalin is a potential regimen to be used in combination with conventional chemotherapeutic drugs to improve acute promyelocytic leukemia therapy.
背景与目的
蟾毒灵是从中国蟾蜍毒液制剂蟾酥中分离得到的强心甾体，已证明在某些实验条件下可诱导白血病细胞分化和凋亡。然而，蟾毒灵诱导急性早幼粒细胞白血病细胞凋亡的详细机制在很大程度上仍未被探索。
方法
用蟾毒灵处理急性早幼粒细胞白血病细胞系 NB4，然后通过细胞活力测定评估增殖，通过流式细胞术分析检测凋亡。此外，用 MEK 抑制剂 PD98059 联合蟾毒灵处理 NB4 细胞，通过 Western blot 分析检测 survivin 的表达和 caspase-3 的激活。
结果
蟾毒灵呈剂量和时间依赖性抑制 NB4 细胞的增殖并诱导其凋亡。此外，蟾毒灵与 PD98059 协同抑制 NB4 细胞的增殖并诱导其凋亡，这与 survivin 表达下调和 caspase-3 激活上调有关。
结论
蟾毒灵可能与常规化疗药物联合用于改善急性早幼粒细胞白血病的治疗。
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