Bai Ding-Ping, Zhang Xi-Feng, Zhang Guo-Liang, Huang Yi-Fan, Gurunathan Sangiliyandi
Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University, Fuzhou, China.
College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
Int J Nanomedicine. 2017 Sep 5;12:6521-6535. doi: 10.2147/IJN.S140071. eCollection 2017.
Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3).
ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays.
Exposure of cells to ZnO NPs resulted in a dose-dependent loss of cell viability, and the characteristic apoptotic features such as rounding and loss of adherence, enhanced reactive oxygen species generation, and loss of mitochondrial membrane potential were observed in the ZnO NP-treated cells. Furthermore, the cells treated with ZnO NPs showed significant double-strand DNA breaks, which are gained evidences from significant number of γ-HAX and Rad51 expressed cells. ZnO NP-treated cells showed upregulation of p53 and LC3, indicating that ZnO NPs are able to upregulate apoptosis and autophagy. Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-HAX, p53, and LC3 and downregulation of Bcl-2.
The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades.
氧化锌纳米颗粒（ZnO NPs）常用于油漆、表面涂层和化妆品等工业产品中，最近，它们也被用于生物和生物医学应用的研究。因此，本研究旨在探讨ZnO NPs对人卵巢癌细胞（SKOV3）的细胞毒性、凋亡和自噬的影响。
采用紫外可见光谱、X射线衍射、透射电子显微镜、傅里叶变换红外光谱和原子力显微镜等多种分析技术对晶体尺寸为20 nm的ZnO NPs进行表征。通过一系列细胞实验检测细胞毒性、凋亡和自噬。
细胞暴露于ZnO NPs导致细胞活力呈剂量依赖性丧失，在ZnO NP处理的细胞中观察到典型的凋亡特征，如细胞变圆和黏附丧失、活性氧生成增加以及线粒体膜电位丧失。此外，用ZnO NPs处理的细胞显示出明显的双链DNA断裂，这从大量表达γ-HAX和Rad51的细胞中得到了证据。ZnO NP处理的细胞显示p53和LC3上调，表明ZnO NPs能够上调凋亡和自噬。最后，蛋白质印迹分析显示Bax、caspase-9、Rad51、γ-HAX、p53和LC3上调，Bcl-2下调。
研究结果表明，ZnO NPs能够通过产生活性氧和氧化应激在人卵巢细胞中诱导显著的细胞毒性、凋亡和自噬。因此，本研究表明，ZnO NPs因其具有良好的带隙、静电荷、表面化学性质以及增强氧化还原循环级联反应等多个有利特性，是合适的固有抗癌剂。
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