科研之友
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摘要
Arsenic trioxide (As2O3) has been reported to have potent antitumor effects in vitro and in vivo by inducing cell death via cell cycle arrest and apoptosis in leukemia cells, but the mechanisms of As2O3-mediated cell death are not fully understood. In this study, we provided in vitro evidence that As2O3 was a potent inducer of autophagy in leukemia K562 and its drug-resistant line K562/ADM cells. As2O3 significantly activated autophagic cell death (programmed cell death type II) in leukemia cell lines. Numerous large cytoplasmic inclusions, abundant autophagic vacuoles, phagocytizing cytoplasm and organelles were observed in As2O3-treated cells using electron microscope. MDC-labeled autophagic vacuoles were observed by fluorescent inverted phase contrast microscopy and the enhanced MDC fluorescent staining was detected by flow cytometry in As2O3-treated cells. Furthermore, real-time quantitative RT-PCR revealed that the expression levels of Beclin-1 and LC3 genes, which play key roles in autophagy, increased in As2O3 treated samples than in controls, indicating that autophagy can potentially be involved in the antitumor properties of As2O3. The expression level of Bcl-2 gene, an anti-apoptotic molecule, decreased in As2O3 treated samples than in controls, suggesting that Bcl-2 may be involved in accumulating Beclin-1 and triggering autophagic cell death in As2O3-treated leukemia cells. Western blotting also showed that As2O3 up-regulated Beclin-1. Altogether, our data provide direct evidence that autophagic cell death is critical for the effects of As2O3 on acute myelogenous leukemia cells.
- 出版日期2012-9
- 单位兰州大学
