Apo2L和足叶乙甙、阿糖胞苷体外协同抑制白血病细胞增殖

目的 研究化疗药足叶乙甙(Vp16)或阿糖胞苷(Ara-C)上调HL-60细胞DR5基因表达，并增强凋亡素2配体(Apo2L)诱导HL-60细胞凋亡的作用。方法 通过AnnexinⅤ／PI染色，流式细胞仪检测HL-60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-60细胞DR5基因表达的变化。结果①Apo2L能诱导HL-60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；③Vpl6或Ara-C能上调HL-60细胞DR5基因表达，Vp16或Ara—C可和Apo2L协同诱导HL-60细胞凋亡。结论 Apo2L能诱导HL-60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-60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。

Synergetic effect of Apo2L and chemotherapeutic agents on leukemia cells

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 staining, 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: 1. Apo2L induced apoptosis of HL-60 cells in a dose-dependent manner. 2. Apo2L inhibited the proliferation of fresh leukemia cells, but there was difference among different subtypes. 3. Vp16 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.