Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Majmaah University, AL-Majmaah, 11932, Saudi Arabia.
Int J Nanomedicine. 2022 May 18;17:2261-2281. doi: 10.2147/IJN.S355408. eCollection 2022.
Zinc oxide nanoparticles (ZnO NPs) show anti-cancer activity. Diffuse Large B-cell Lymphoma (DLBCL) is a type of B-cell malignancies with unsatisfying treatment outcomes. This study was set to assess the potential of ZnO NPs to selectively induce apoptosis in human DLBCL cells (OCI-LY3), and to describe possible molecular mechanisms of action.
The impact of ZnO NPs on DLBCL cells and normal peripheral blood mononuclear cells (PBMCs) was studied using cytotoxicity assay and flow-cytometry. Transcriptomics analysis was conducted to identify ZnO NPs-dependent changes in the transcriptomic profiles of DLBCL cells.
ZnO NPs selectively induced apoptosis in DLBCL cells, and caused changes in their transcriptomes. Deferential gene expression (DGE) with fold change (FC) ≥3 and p ≤ 0.008 with corrected p ≤ 0.05 was identified for 528 genes; 125 genes were over-expressed and 403 genes were under-expressed in ZnO NPs-treated DLBCL cells. The over-expressed genes involved in biological processes and pathways like stress response to metal ion, cellular response to zinc ion, metallothioneins bind metals, oxidative stress, and negative regulation of growth. In contrast, the under-expressed genes were implicated in DNA packaging complex, signaling by NOTCH, negative regulation of gene expression by epigenetic, signaling by WNT, M phase of cell cycle, and telomere maintenance. Setting the FC to ≥1.5 with p ≤ 0.05 and corrected p ≤ 0.1 showed ZnO NPs to induce over-expression of anti-oxidant genes and under-expression of oncogenes; target B-cell receptor (BCR) signaling pathway and NF-κB pathway; and promote apoptosis by intrinsic and extrinsic pathways.
Overall, ZnO NPs selectively induced apoptosis in DLBCL cells, and possible molecular mechanisms of action were described.
氧化锌纳米粒子（ZnO NPs）具有抗癌活性。弥漫性大 B 细胞淋巴瘤（DLBCL）是一种 B 细胞恶性肿瘤，治疗效果不尽如人意。本研究旨在评估 ZnO NPs 选择性诱导人 DLBCL 细胞（OCI-LY3）凋亡的潜力，并描述其可能的作用机制。
通过细胞毒性测定和流式细胞术研究 ZnO NPs 对 DLBCL 细胞和正常外周血单个核细胞（PBMCs）的影响。进行转录组学分析，以确定 ZnO NPs 对 DLBCL 细胞转录组谱的影响。
ZnO NPs 选择性诱导 DLBCL 细胞凋亡，并导致其转录组发生变化。差异基因表达（DGE）的倍数变化（FC）≥3，p≤0.008，校正后的 p≤0.05，共鉴定出 528 个基因；在 ZnO NPs 处理的 DLBCL 细胞中，有 125 个基因上调，403 个基因下调。上调的基因参与应激反应金属离子、细胞对锌离子的反应、金属硫蛋白结合金属、氧化应激、生长的负调控等生物学过程和途径；而下调的基因与 DNA 包装复合物、NOTCH 信号转导、表观遗传调控基因表达、WNT 信号转导、细胞周期 M 期和端粒维持有关。将 FC 设置为≥1.5，p≤0.05，校正后 p≤0.1，结果显示 ZnO NPs 诱导抗氧化基因上调和癌基因下调；靶向 B 细胞受体（BCR）信号通路和 NF-κB 通路；并通过内在和外在途径促进细胞凋亡。
总体而言，ZnO NPs 选择性诱导 DLBCL 细胞凋亡，并描述了可能的作用机制。
Zotero 插件
