Induced effect of zinc oxide nanoparticles on human acute myeloid leukemia cell apoptosis by regulating mitochondrial division
Induced effect of zinc oxide nanoparticles on human acute myeloid leukemia cell apoptosis by regulating mitochondrial division
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DOI：
10.1002/iub.2615
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发表时间：
2022-04
期刊：
影响因子：
4.6
通讯作者：
Xuewei Yin;Zonghong Li;C. Lyu;Yan Wang;Shumin Ding;Chenchen Ma;Jing-yi Wang;S. Cui;Jinxin Wang;Dadong Guo;R. Xu
中科院分区：
文献类型：
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作者：
Xuewei Yin;Zonghong Li;C. Lyu;Yan Wang;Shumin Ding;Chenchen Ma;Jing-yi Wang;S. Cui;Jinxin Wang;Dadong Guo;R. Xu
氧化锌纳米颗粒具有良好的抗肿瘤作用，本研究旨在阐明氧化锌纳米颗粒通过调节线粒体分裂诱导急性髓系白血病细胞凋亡的机制。将急性髓系白血病细胞系THP-1细胞与不同浓度的纳米氧化锌孵育24小时。检测DRP-1、Bc l-2、Bax基因和蛋白的表达，并检测纳米氧化锌对THP-1细胞的活性氧(ROS)、线粒体膜电位(Δψm)、细胞凋亡率和ATP生成的影响。此外，还检测了DRP-1抑制剂Mdivi-1和氧化锌纳米粒对THP-1细胞的影响。结果表明，随着纳米氧化锌浓度的增加和孵育时间的延长，THP-1细胞存活率下降，且呈剂量和时间依赖性。氧化锌纳米粒可降低细胞Δψm和ATPm水平，诱导ROS产生，增加线粒体分裂和凋亡水平。相反，经DRP-1抑制剂干预后，THP-1细胞的凋亡率明显降低，提示氧化锌纳米粒可通过调节线粒体分裂诱导THP-1细胞的凋亡。综上所述，纳米氧化锌有望为临床治疗急性髓系白血病提供新的依据和思路。
Zinc oxide nanoparticles (ZnO NPs) have exhibited excellent anti‐tumor properties; the present study aimed to elucidate the underlying mechanism of ZnO NPs induced apoptosis in acute myeloid leukemia (AML) cells by regulating mitochondrial division. THP‐1 cells, an AML cell line, were first incubated with different concentrations of ZnO NPs for 24 hr. Next, the expression of Drp‐1, Bcl‐2, Bax mRNA, and protein was detected, and the effects of ZnO NPs on the levels of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), apoptosis, and ATP generation in THP‐1 cells were measured. Moreover, the effect of Drp‐1 inhibitor Mdivi‐1 and ZnO NPs on THP‐1 cells was also detected. The results showed that the THP‐1 cells survival rate decreased with the increment of ZnO NPs concentration and incubation time in a dose‐ and time‐dependent manner. ZnO NPs can reduce the cell Δψm and ATP levels, induce ROS production, and increase the levels of mitochondrial division and apoptosis. In contrast, the apoptotic level was significantly reduced after intervention of Drp‐1 inhibitor, suggesting that ZnO NPs can induce the apoptosis of THP‐1 cells by regulating mitochondrial division. Overall, ZnO NPs may provide a new basis and idea for treating human acute myeloid leukemia in clinical practice.