Nrf2/ARE途径在紫草素诱导U937细胞分化中的作用

Effect of Nrf2/ARE pathway on Shikonin induced U937 cell lines differentiation

目的研究紫草素诱导U937细胞分化及其相关机制。方法通过网络药理学分析紫草素潜在靶点相互作用。紫草素处理U937细胞,进行细胞活力、形态观察、NBT还原能力、Nrf2分化相关基因及Nrf2途径相关分子mRNA表达和核蛋白含量检测。结果紫草素靶点影响Nrf2途径,并且Nrf2能通过蛋白质互作影响分化。紫草素显著抑制U937细胞增殖,升高NBT还原能力、CD11b和CD14mRNA表达、Nrf2核蛋白含量、Nrf2及其下游基因mRNA的表达量。上调细胞Nrf2/ARE途径,增加CD11b和CD14mRNA表达,反之则降低其表达。结论紫草素上调Nrf2/ARE途径增强诱导人急性髓系白血病U937细胞分化。

Objective To investigate the effect and disclose its potential mechanisms of shikonin on poliferation and differentiation in human lymphoma cells. Methods Latent relationship between targets of shikonin and Nrf2 pathway were expound via protein-protein interaction network. cell viability,morphological changes,NBT reduction activity,the expression of Nrf2 and its downstream genes and content of Nrf2 nuclear protein were measured with after shikonin treatment. Results The targets of shikonin affected the Nrf2 / ARE pathway through protein interaction network,Nrf2 affected differentiation through protein interaction network. Compared with normal control group,the inhibition ratio,reduction capacity to NBT,Nrf2 nuclear protein content,levels of CD11 b,CD14,Nrf2,and its downstream genes were higher in the U937 cells induced by shikonin. The mRNA expression levels of CD11 b and CD14 were significantly increased after activation of Nrf2 pathway,which could be reversed with Nrf2 inhibitor.Conclusion Shikonin induces cell differentiation by up-regulating Nrf2 pathway in U937 cell lines.