Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Molecular Medicine Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Biomed Res Int. 2024 Feb 19;2024:7145339. doi: 10.1155/2024/7145339. eCollection 2024.
Silver nanoparticles (AgNPs) are known as one of the highly utilized NPs owing to their unique characteristics in the field of cancer research. The goal of this research was to explore the oxidative stress, apoptosis, and angiogenesis in SKBR3 breast cancer cells after exposure to AgNPs. The survival rate of SKBR3 cancer cells and MCF-10A normal breast cells was assessed under the effects of different concentrations (0, 32, 64, 128, and 250 g/ml) by MTT method. The oxidative condition was assessed by measuring reactive oxygen species (ROS) production, total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), and antioxidant enzyme activity (CAT, GPx, and CAT) using colorimetric-based kits. Flow cytometry and Hoechst 33258 staining were performed to investigate the induction of apoptosis. Furthermore, the expression of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and caspase 3 and 7 activity was measured. The cell migration and vascular endothelial growth factor-A (VEGF-A) gene expression, protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K) were also studied. The MTT results indicated that AgNPs inhibit the SKBR3 cells' viability in a concentration-dependent way. Besides, AgNPs markedly induced oxidative stress via increasing TOS content, MDA production, reduction of TAC, and regulation of antioxidant enzyme level. Additionally, AgNPs promoted apoptosis as revealed by an enhancement in Bax/Bcl-2 expression ratio. Findings also indicated that AgNPs suppress the expression of genes (VEGF-A, AKT, and PI3K) involved in angiogenesis. Altogether, our data revealed that AgNPs initiate oxidative stress and apoptosis in SKBR3 breast cancer cells, dose dependently.
纳米银颗粒(AgNPs)由于其在癌症研究领域的独特特性而被广泛应用。本研究旨在探讨 AgNPs 暴露后 SKBR3 乳腺癌细胞的氧化应激、细胞凋亡和血管生成。采用 MTT 法评估不同浓度(0、32、64、128 和 250μg/ml)AgNPs 对 SKBR3 癌细胞和 MCF-10A 正常乳腺细胞存活率的影响。通过比色法试剂盒测定活性氧(ROS)生成、总氧化剂状态(TOS)、总抗氧化能力(TAC)、丙二醛(MDA)和抗氧化酶活性(CAT、GPx 和 CAT)来评估氧化状态。采用流式细胞术和 Hoechst 33258 染色法研究细胞凋亡的诱导。此外,还测定了 B 细胞淋巴瘤 2 相关 X 蛋白(Bax)、B 细胞淋巴瘤 2(Bcl-2)和 caspase 3 和 7 活性的表达。还研究了细胞迁移和血管内皮生长因子-A(VEGF-A)基因表达、蛋白激酶 B(AKT)、磷脂酰肌醇 3-激酶(PI3K)。MTT 结果表明,AgNPs 以浓度依赖的方式抑制 SKBR3 细胞的活力。此外,AgNPs 通过增加 TOS 含量、MDA 生成、降低 TAC 和调节抗氧化酶水平显著诱导氧化应激。此外,AgNPs 促进细胞凋亡,表现为 Bax/Bcl-2 表达比值增加。研究结果还表明,AgNPs 抑制了参与血管生成的基因(VEGF-A、AKT 和 PI3K)的表达。总之,我们的数据表明,AgNPs 以剂量依赖的方式在 SKBR3 乳腺癌细胞中引发氧化应激和细胞凋亡。
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