Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.
Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China.
Int J Environ Health Res. 2024 Jan;34(1):150-165. doi: 10.1080/09603123.2022.2134559. Epub 2022 Oct 20.
Arsenic has been identified as a carcinogen, although the molecular mechanism underlying itscarcinogenesis has not been fully elucidated. To date, only a few studies have attempted to confirm a direct link between oxidative stress and the Warburg effect . This study demonstrated that 0.2 μmol/L As induced the Warburg effect to contribute to abnormal proliferation of L-02 cells, that was mediated by upregulation of hexokinase 2 (HK2), a key enzyme in glycolysis. Further study indicated that arsenic-induced accumulation of reactive oxygen species (ROS) activated the nuclear factor kappa B (NF-κB) signaling pathway by phosphorylation of p65 at the Ser536 and Ser276 sites, leading to upregulated expression of HK2. We therefore concluded that the ROS/NF-κB/HK2 axis contributes to the Warburg effect and cell proliferation induced by low doses of arsenic.ROS, Reactive oxygen species; NAC, -acetyl-L-cysteine; 2-DG, 2-deoxy-D-glucose; 2-NBDG, 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose.
砷已被确定为一种致癌物质，尽管其致癌作用的分子机制尚未完全阐明。迄今为止，只有少数研究试图证实氧化应激与瓦博格效应之间的直接联系。本研究表明，0.2μmol/L 的砷诱导瓦博格效应导致 L-02 细胞异常增殖，这是通过糖酵解关键酶己糖激酶 2（HK2）的上调介导的。进一步的研究表明，砷诱导的活性氧（ROS）积累通过 Ser536 和 Ser276 位点的磷酸化激活核因子 kappa B（NF-κB）信号通路，导致 HK2 的表达上调。因此，我们得出结论，ROS/NF-κB/HK2 轴有助于低剂量砷诱导的瓦博格效应和细胞增殖。ROS，活性氧；NAC，N-乙酰-L-半胱氨酸；2-DG，2-脱氧-D-葡萄糖；2-NBDG，2-脱氧-2-[(7-硝基-2,1,3-苯并恶二唑-4-基)氨基]-D-葡萄糖。
