Division of Nanobiotechnology, Warsaw University of Life Science, Ciszewskiego 8, 02-786, Warsaw, Poland.
Department of Veterinary and Animal Sciences, University of Copenhagen, Groennegaardsvej 3, 1870, Frederiksberg, Denmark.
Sci Rep. 2018 Oct 3;8(1):14733. doi: 10.1038/s41598-018-33179-3.
Gliomas develop an expanded vessel network and a microenvironment characterized by an altered redox environment, which produces high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that fuel its growth and malignancy. ROS and RNS can influence tumor cell malignancy via the redox-regulated transcription factor NF-κB, whose activation is further regulated by the mutation status of p53. The objective of this study was to assess the influence of graphite nanoparticles (NG) and graphene oxide nanoplatelets (nGO) on the angiogenic potential of glioma cell lines with different p53 statuses. Nanoparticle treatment of glioma cells decreased the angiogenesis of human umbilical vein endothelial cells (HUVEC) cocultured with U87 (p53 wild type) and was not effective for U118 (p53 mutant) cells. Nanoparticle activity was related to the decreased level of intracellular ROS and RNS, which downregulated NF-κB signaling depending on the p53 status of the cell line. Activation of NF-κB signaling affected downstream protein levels of interleukin 6, interleukin 8, growth-regulated oncogene α, and monocyte chemotactic protein 1. These results indicate that the activity of NG and nGO can be regulated by the mutation status of glioma cells and therefore give new insights into the use of nanoparticles in personalized biomedical applications regarding glioma angiogenesis and its microenvironment.
神经胶质瘤会发展出一个扩张的血管网络和一个以氧化还原环境改变为特征的微环境，从而产生高水平的活性氧（ROS）和活性氮（RNS），这些物质会促进其生长和恶性转化。ROS 和 RNS 可以通过氧化还原调节转录因子 NF-κB 影响肿瘤细胞的恶性程度，而 NF-κB 的激活进一步受到 p53 突变状态的调节。本研究的目的是评估石墨纳米颗粒（NG）和石墨烯氧化物纳米片（nGO）对具有不同 p53 状态的神经胶质瘤细胞系血管生成潜力的影响。纳米颗粒处理降低了与 U87（野生型 p53）共培养的人脐静脉内皮细胞（HUVEC）的血管生成能力，而对 U118（p53 突变型）细胞则无效。纳米颗粒的活性与细胞内 ROS 和 RNS 水平的降低有关，这取决于细胞系的 p53 状态，从而下调了 NF-κB 信号通路。NF-κB 信号通路的激活会影响白细胞介素 6、白细胞介素 8、生长调节癌基因α和单核细胞趋化蛋白 1 的下游蛋白水平。这些结果表明，NG 和 nGO 的活性可以通过神经胶质瘤细胞的突变状态来调节，从而为纳米颗粒在针对神经胶质瘤血管生成及其微环境的个性化生物医学应用中的应用提供了新的见解。
