Department of Public Health, School of Medicine, Shihezi University, Shihezi 832000, Xinjiang, China.
Department of Maternal and Children Health, School of Public Health, Capital Medical University, Beijing 100069, China.
Curr Pharm Des. 2022;28(31):2583-2599. doi: 10.2174/1381612828666220818150959.
We aimed to systematically evaluate the regulatory effect of arsenic on DNMTs and its downstream molecules in tumor cells and to provide a theoretical framework revealing the specific mechanism of arsenic in the treatment of tumors.
Meta-analysis was performed using RevMan 5.3 and Stata 12.0, and differences between groups were described as standardized mean difference.
We found out that compared with the control group, the expression of DNMT1, DNMT3a, DNMT3b, MMP-9 & β-catenin decreased and the expression of RECK and E-cadherin increased in the arsenic-treated group. Subgroup analysis showed that high-dose arsenic exposure (> 2 μmol/L) reduced the expression of DNMT1, DNMT3b, MMP-9, and β-catenin and promoted the expression of E-cadherin. Arsenic could decrease the level of DNMT1, MMP-9 & β-catenin and increase the level of E-cadherin with short-time arsenic intervention (≤ 48 h). Arsenic could reduce DNMT1, DNMT3a, DNMT3b & β-catenin in hematological tumor cells; under the effect of arsenic, the expression of DNMT1, DNMT3b, MMP-9 & β-catenin decreased in solid tumor cells. In addition, the regulation of arsenic on DNMT3a was dose-dependent in the range of arsenic concentration from 0 to 5.0 μmol/L. The dose, time, and cell types of arsenic intervention were the variables of heterogeneity.
Arsenic could inhibit the proliferation and viability of tumor cells, and its mechanism may be related to the reduction of DNMTs and regulation of the expression of its downstream molecules. Overall, arsenic may be a promising candidate for the treatment of tumors.
本研究旨在系统评估砷对肿瘤细胞中 DNMTs 及其下游分子的调控作用，为揭示砷治疗肿瘤的具体机制提供理论框架。
采用 RevMan 5.3 和 Stata 12.0 进行 Meta 分析，组间差异采用标准化均数差表示。
与对照组相比，砷处理组中 DNMT1、DNMT3a、DNMT3b、MMP-9 和β-catenin 的表达降低，RECK 和 E-cadherin 的表达升高。亚组分析显示，高剂量砷暴露（>2 μmol/L）降低了 DNMT1、DNMT3b、MMP-9 和β-catenin 的表达，促进了 E-cadherin 的表达。砷干预（≤48 h）短时间内可降低 DNMT1、MMP-9 和β-catenin 的水平，增加 E-cadherin 的水平。砷可降低血液肿瘤细胞中 DNMT1、DNMT3a、DNMT3b 和β-catenin 的水平，在砷的作用下，固体肿瘤细胞中 DNMT1、DNMT3b、MMP-9 和β-catenin 的表达降低。此外，在砷浓度为 0 至 5.0 μmol/L 的范围内，砷对 DNMT3a 的调节呈剂量依赖性。砷干预的剂量、时间和细胞类型是异质性的变量。
砷可抑制肿瘤细胞的增殖和活力，其机制可能与 DNMTs 的减少及其下游分子表达的调节有关。总的来说，砷可能是治疗肿瘤的一种有前途的候选药物。
