Apo2L和足叶乙甙、阿糖胞苷体外协同抑制白血病细胞增殖

Synergetic effect of Apo2L and chemotherapeutic agents on leukemia cells

目的 研究化疗药足叶乙甙 (Vp16 )或阿糖胞苷 (Ara C)上调HL 6 0细胞DR5基因表达 ,并增强凋亡素 2配体 (Apo2L)诱导HL 6 0细胞凋亡的作用。方法 通过AnnexinⅤ /PI染色 ,流式细胞仪检测HL 6 0细胞的凋亡率 ;通过MTT试验检测Apo2L对白血病原代细胞的生长抑制率 ;利用半定量RT PCR检测HL 6 0细胞DR5基因表达的变化。结果 ①Apo2L能诱导HL 6 0细胞凋亡 ,存在剂量 效应关系 ;②Apo2L能抑制白血病原代细胞生长 ,但不同类型原代细胞敏感性存在明显差异 ;③Vp16或Ara C能上调HL 6 0细胞DR5基因表达 ,Vp16或Ara C可和Apo2L协同诱导HL 6 0细胞凋亡。结论 Apo2L能诱导HL 6 0细胞凋亡 ,抑制白血病原代细胞生长 ;化疗药Vp16或Ara C能上调HL 6 0细胞DR5基因表达 ,并增强Apo2L的诱导细胞凋亡作用 ;Apo2L有可能成为一种新型抗肿瘤制剂。

Objective To explore if the antileukemic drugs Vp16 or Ara-C are able to upregulate DR5 gene expression and enhance Apo2L-induced apoptosis of HL-60 cells. Methods Cell apoptosis was determined by flow cytometry after annexin V/PI stainning, the effect of Apo2L on fresh leukemia cells by MTT reduction assay, the expression of DR5 gene in HL-60 cells by semi-quantitative RT-PCR. Results ①Apo2L induced apoptosis of HL-60 cells in a dose-dependent manner. ②Apo2L inhibited the proliferation of fresh leukemia cells, but there was difference among different subtypes. ③Vp16 or Ara-C upregulated DR5 gene expression and augmented Apo2L-induced apoptosis in HL-60 cells. Conclusion Apo2L could induce apoptosis of HL-60 cells and inhibit the proliferation of fresh leukemia cells. Ara-C or Vp16 upregulated DR5 gene expression and increased the sensitivity of HL-60 to Apo2L-induced cytotoxicity. Apo2L might be a promising antileukemic agent for the treatment of leukemia.