利用角豆提取物的绿色合成氧化锌纳米粒子的抗乳腺癌作用。
The Anti-Breast Cancer Effects of Green-Synthesized Zinc Oxide Nanoparticles Using Carob Extracts.
机构信息
Department of Biochemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
出版信息
Anticancer Agents Med Chem. 2021;21(3):316-326. doi: 10.2174/1871520620666200721132522.
BACKGROUND
The use of nanoparticles synthesized by the green method to treat cancer is fairly recent. The aim of this study was to evaluate cytotoxicity, apoptotic and anti-angiogenic effects and the expression of involved genes, of Zinc Oxide Nanoparticles (ZnO-NPs) synthesized with Carob extracts on different human breast cancer cell lines.
METHODS
ZnO-NPs were synthesized using the extracts of Carob and characterized with various analytical techniques. The MCF-7 and MDA-MB231 cells were treated at different times and concentrations of ZnO-NPs. The cytotoxicity, apoptosis, and anti-angiogenic effects were examined using a series of cellular assays. Expression of apoptotic genes (Bax and Bcl2) and anti-angiogenic genes, Vascular Endothelial Growth Factor (VEGF) and its Receptor (VEGF-R) in cancer cells treated with ZnO-NPs were examined with Reverse Transcriptionquantitative Polymerase Chain Reaction (RT-qPCR). The anti-oxidant activities of ZnO-NPs were evaluated by ABTS and DPPH assay.
RESULTS
Exposure of cells to ZnO-NPs resulted in a dose-dependent loss of cell viability. The IC50 values at 24, 48, and 72 hours were 125, 62.5, and 31.2μg/ml, respectively (p<0.001). ZnO-NPs treated cells showed, in fluorescent microscopy, that ZnO-NPs are able to upregulate apoptosis and RT-qPCR revealed the upregulation of Bax (p<0.001) and downregulation of Bcl-2 (p<0.05). ZnO-NPs increased VEGF gene expression while decreasing VEGF-R (p<0.001). The anti-oxidant effects of ZnO-NPs were higher than the control group and were dose-dependent (p<0.001).
CONCLUSION
ZnO-NPs synthetized using Carob extract have the ability to eliminate breast cancer cells and inhibit angiogenesis, therefore, they could be used as an anticancer agent.
背景
使用通过绿色方法合成的纳米粒子来治疗癌症是相当新的。本研究的目的是评估 Carob 提取物合成的氧化锌纳米粒子（ZnO-NPs）对不同人乳腺癌细胞系的细胞毒性、凋亡和抗血管生成作用以及相关基因的表达。
方法
使用 Carob 提取物合成 ZnO-NPs，并通过各种分析技术对其进行表征。将 MCF-7 和 MDA-MB231 细胞用不同浓度和时间的 ZnO-NPs 处理。使用一系列细胞检测来检查细胞毒性、凋亡和抗血管生成作用。用逆转录定量聚合酶链反应（RT-qPCR）检测经 ZnO-NPs 处理的癌细胞中凋亡基因（Bax 和 Bcl2）和抗血管生成基因血管内皮生长因子（VEGF）及其受体（VEGF-R）的表达。通过 ABTS 和 DPPH 测定评估 ZnO-NPs 的抗氧化活性。
结果
细胞暴露于 ZnO-NPs 导致细胞活力呈剂量依赖性下降。24、48 和 72 小时的 IC50 值分别为 125、62.5 和 31.2μg/ml（p<0.001）。荧光显微镜下，ZnO-NPs 处理的细胞能够上调细胞凋亡，RT-qPCR 显示 Bax 上调（p<0.001），Bcl-2 下调（p<0.05）。ZnO-NPs 增加了 VEGF 基因的表达，同时降低了 VEGF-R（p<0.001）。ZnO-NPs 的抗氧化作用高于对照组，且呈剂量依赖性（p<0.001）。
结论
使用 Carob 提取物合成的 ZnO-NPs 具有消除乳腺癌细胞和抑制血管生成的能力，因此可作为抗癌剂。
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