Although accumulating evidence has revealed that metallothioneins (MTs) and its family member MT2A are strongly linked to the risk of various solid tumors, researches on the occurrence and development of acute myeloid leukemia (AML) have rarely been investigated. Here, we constructed a lentiviral vector with MT2A over-expression and the interfering plasmids with MT2A expression inhibition to study the influence of MT2A on the bioactivities of HL60 cells. After cells were infected with a lentiviral vector containing the MT2A gene, both transcription and translation levels of MT2A were significantly increased in the over-expressed group in comparison with control groups. In vitro experiments, all results demonstrated that cell reproductive capacity was inhibited, but cell apoptosis rate was significantly increased. Together, the expression of apoptosis-related protein Bcl2 was remarkably reduced, while a high expression level of Bax protein was detected. Further experiments revealed that up-regulation of MT2A induced cell apoptosis and promoted G2/M phase arrest. The mechanism may be associated with down-regulated p-IκB-α and cyclinD1 expression and up-regulated IκB-α expression in the nuclear factor-kappaB (NF-κB) pathway. On the contrary, MT2A expression was down-regulated by interfering plasmids. We found that cell proliferative potential was notably increased in the interfering group compared with the negative and untreated group. What's more, MT2A may be closely related to AML cell proliferation and function via the NF-κB signal pathway.

中文翻译：

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MT2A对HL60细胞凋亡和增殖的影响

尽管越来越多的证据表明金属硫蛋白（MTs）及其家族成员MT2A与各种实体瘤的发病风险密切相关，但对急性髓系白血病（AML）的发生发展的研究却鲜有研究。在这里，我们构建了具有 MT2A 过表达的慢病毒载体和具有 MT2A 表达抑制的干扰质粒，以研究 MT2A 对 HL60 细胞生物活性的影响。用含有 MT2A 基因的慢病毒载体感染细胞后，与对照组相比，过表达组中 MT2A 的转录和翻译水平均显着增加。在体外实验中，所有结果都表明细胞繁殖能力受到抑制，但细胞凋亡率显着增加。一起，凋亡相关蛋白Bcl2的表达显着降低，同时检测到Bax蛋白的高表达。进一步的实验表明，MT2A 的上调诱导细胞凋亡并促进 G2/M 期阻滞。该机制可能与核因子-κB (NF-κB) 通路中 p-IκB-α 和细胞周期蛋白 D1 表达下调和 IκB-α 表达上调有关。相反，MT2A 表达被干扰质粒下调。我们发现与阴性和未处理组相比，干扰组的细胞增殖潜力显着增加。此外，MT2A可能通过NF-κB信号通路与AML细胞增殖和功能密切相关。进一步的实验表明，MT2A 的上调诱导细胞凋亡并促进 G2/M 期阻滞。该机制可能与核因子-κB (NF-κB) 通路中 p-IκB-α 和细胞周期蛋白 D1 表达下调和 IκB-α 表达上调有关。相反，MT2A 表达被干扰质粒下调。我们发现与阴性和未处理组相比，干扰组的细胞增殖潜力显着增加。此外，MT2A可能通过NF-κB信号通路与AML细胞增殖和功能密切相关。进一步的实验表明，MT2A 的上调诱导细胞凋亡并促进 G2/M 期阻滞。该机制可能与核因子-κB (NF-κB) 通路中 p-IκB-α 和细胞周期蛋白 D1 表达下调和 IκB-α 表达上调有关。相反，MT2A 表达被干扰质粒下调。我们发现与阴性和未处理组相比，干扰组的细胞增殖潜力显着增加。此外，MT2A可能通过NF-κB信号通路与AML细胞增殖和功能密切相关。该机制可能与核因子-κB (NF-κB) 通路中 p-IκB-α 和细胞周期蛋白 D1 表达下调和 IκB-α 表达上调有关。相反，MT2A 表达被干扰质粒下调。我们发现与阴性和未处理组相比，干扰组的细胞增殖潜力显着增加。此外，MT2A可能通过NF-κB信号通路与AML细胞增殖和功能密切相关。该机制可能与核因子-κB (NF-κB) 通路中 p-IκB-α 和细胞周期蛋白 D1 表达下调和 IκB-α 表达上调有关。相反，MT2A 表达被干扰质粒下调。我们发现与阴性和未处理组相比，干扰组的细胞增殖潜力显着增加。此外，MT2A可能通过NF-κB信号通路与AML细胞增殖和功能密切相关。