Irannejad Fatemeh, Shahbazi Shahrzad, Reiisi Somayeh, Heidari Razieh
Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran.
Division of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Med Oncol. 2025 Jan 6;42(2):39. doi: 10.1007/s12032-024-02593-1.
Reactive oxygen species (ROS) generated by oxidative stress have emerged as critical factors in the pathophysiology of malignancies. This study investigated the antioxidant and anticancer properties of zinc (Zn), selenium (Se), and silver (Ag) nanoparticles (NPs) against the A2780 human ovarian cancer cell line. Here, the bioinformatics approach was used to determine the top differentially expressed genes associated with oxidative stress. The ZnO-, Se-, and Ag-NPs were then synthesized via a green synthesis method and subsequently characterized using techniques, such as FTIR, XRD, DLS, zeta potential analysis, FESEM, and TEM. The antioxidant capacity of the NPs was evaluated using a DPPH scavenging assay and their effect on superoxide dismutase enzyme activity was determined. HDF and A2780 cells were treated with varying concentrations of ZnO-, Se-, and Ag-NPs, and cell viability and colony formation were assessed using MTT and clonogenic assays, respectively. Additionally, qPCR was performed to analyze the expression of the candidate genes NOX4, SOD2, and NR4A4. Characterization techniques confirmed the successful synthesis of pure, crystalline, and spherical NPs. Antioxidant assays demonstrated the significant antioxidant properties of ZnO-, Se-, and Ag-NPs. In vitro studies indicated that ZnO-, Se-, and Ag-NPs effectively inhibited cell proliferation and suppressed colony formation, likely owing to the downregulation of NOX4 and upregulation of SOD2 genes. Our findings suggest that ZnO-, Se-, and Ag-NPs may serve as promising anticancer agents for ovarian cancer and NOX4 downregulation and SOD2 upregulation can be proposed as oxidative stress biomarkers; however, further experimental investigation is required to elucidate the therapeutic potential of NPs and the early detection potential of biomarkers.
氧化应激产生的活性氧（ROS）已成为恶性肿瘤病理生理学中的关键因素。本研究调查了锌（Zn）、硒（Se）和银（Ag）纳米颗粒（NPs）对A2780人卵巢癌细胞系的抗氧化和抗癌特性。在此，采用生物信息学方法确定与氧化应激相关的最显著差异表达基因。然后通过绿色合成方法合成ZnO-、Se-和Ag-NPs，并随后使用傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、动态光散射（DLS）、zeta电位分析、场发射扫描电子显微镜（FESEM）和透射电子显微镜（TEM）等技术对其进行表征。使用DPPH清除试验评估NPs的抗氧化能力，并测定其对超氧化物歧化酶活性的影响。用不同浓度的ZnO-、Se-和Ag-NPs处理人皮肤成纤维细胞（HDF）和A2780细胞，分别使用MTT和克隆形成试验评估细胞活力和集落形成。此外，进行定量聚合酶链反应（qPCR）以分析候选基因NOX4、SOD2和NR4A4的表达。表征技术证实成功合成了纯净、结晶和球形的NPs。抗氧化试验证明了ZnO-、Se-和Ag-NPs具有显著的抗氧化特性。体外研究表明，ZnO-、Se-和Ag-NPs有效抑制细胞增殖并抑制集落形成，这可能是由于NOX4基因下调和SOD2基因上调所致。我们的研究结果表明，ZnO-、Se-和Ag-NPs可能是有前景的卵巢癌抗癌药物，并且可以将NOX4下调和SOD2上调作为氧化应激生物标志物；然而，需要进一步的实验研究来阐明NPs的治疗潜力和生物标志物的早期检测潜力。
