College of Life Sciences and Key Laboratory for Cell Differentiation Regulation, Henan Normal University, Xinxiang, Henan 453007, PR China.
Mol Med Rep. 2011 Nov-Dec;4(6):1327-32. doi: 10.3892/mmr.2011.580. Epub 2011 Sep 1.
The purpose of this study was to investigate the antitumor effects and mechanism of the selenium heteropoly compound (NH₄)₄H₄[Se₂Mo₂V₄O₂₄]·7H₂O (SeMoV) in K562 cells. The results showed that 0.313-10 mg/l SeMoV significantly inhibited the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by a micro-culture tetrazolium assay; the IC50 values were 7.69 and 4.06 mg/l following 48 and 72 h of treatment with SeMoV, respectively. Analysis of the cell cycle indicated that the proportion of cells in the G0/G1 phase was decreased at 48 h whereas the proportion of cells in the S phase was increased following treatment for 24 and 48 h. A significant sub-G1 peak was observed at 5 mg/l for 24 h. Morphological observation revealed typical apoptotic features. SeMoV signifi-cantly caused the accumulation of Ca²⁺, Mg²⁺ and ROS, and a reduction in the pH value and the mitochondrial membrane potential (MMP) in the K562 cells compared with the control (p<0.01), as shown by confocal laser scanning microscopy. Experiments also showed that the expression of Bcl-2 was significantly inhibited by 20 mg/l SeMoV, while Bax expression increased. Meanwhile, the amount of cytochrome C and IκB in K562 cells was increased, while NF-κB expression was significantly decreased, following treatment with SeMoV for 24 h. The experiment implied that SeMoV had antitumor activity and its mechanism was attributed partially to apoptosis, which was induced by the elevation of the intracellular Ca²⁺, Mg²⁺ and ROS concentration, a reduction in the pH value and MMP, and the NF-κB/IκB signaling pathway.
本研究旨在探讨硒杂多化合物（NH₄）₄H₄[Se₂Mo₂V₄O₂₄]·7H₂O（SeMoV）对 K562 细胞的抗肿瘤作用及其机制。结果表明，0.313-10 mg/L SeMoV 能显著抑制 K562 细胞在体外的增殖，呈时间和浓度依赖性；用 SeMoV 处理 48 和 72 h 后，IC50 值分别为 7.69 和 4.06 mg/L。细胞周期分析表明，与对照组相比，48 h 时 G0/G1 期细胞比例降低，24 和 48 h 时 S 期细胞比例增加。24 h 时，5 mg/L 出现明显的亚 G1 峰。形态学观察显示典型的凋亡特征。与对照组相比，SeMoV 能显著引起 K562 细胞内 Ca²⁺、Mg²⁺和 ROS 积聚，pH 值和线粒体膜电位（MMP）降低（p<0.01），这一现象通过共聚焦激光扫描显微镜得到证实。实验还表明，20 mg/L SeMoV 能显著抑制 Bcl-2 的表达，同时增加 Bax 的表达。同时，随着 SeMoV 处理 24 h，K562 细胞中的细胞色素 C 和 IκB 增加，而 NF-κB 表达明显降低。实验表明，SeMoV 具有抗肿瘤活性，其机制部分归因于细胞内 Ca²⁺、Mg²⁺和 ROS 浓度升高、pH 值和 MMP 降低以及 NF-κB/IκB 信号通路诱导的细胞凋亡。
