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通过茴香提取物绿色合成的铜纳米颗粒遵循PI3K/AKT/Mtor信号通路的细胞毒性、抗氧化和抗人肺癌特性的表征与评估。

Characterization and evaluation of the cytotoxic, antioxidant, and anti-human lung cancer properties of copper nanoparticles green-synthesized by fennel extract following the PI3K/AKT/Mtor signaling pathway.

作者信息

Huang Tao, Ma KaiLi, Wang Yihua

机构信息

Department of Oncology, Peking University First Hospital, Taiyuan Hospital, Taiyuan, Shanxi, China.

出版信息

PLoS One. 2025 Jan 9;20(1):e0309207. doi: 10.1371/journal.pone.0309207. eCollection 2025.

Abstract

This work established the cytotoxic, antioxidant and anticancer effects of copper nanoparticles (CuNPs) manufactured with fennel extract, especially on non-small cell lung cancer (NSCLC) as well. CuNPs caused cytotoxicity in a dose-dependent manner for two NSCLC cell lines, A549 and H1650. At 100 μg/ml, CuNPs reduced cell viability to 70% in A549 cells and 65% in H1650 cells. which showed a cytotoxic effect (p<0. 05). Lactate dehydrogenase (LDH) was correspondingly present in a high proportion in the cells, demonstrated upon testing. Together with their cytotoxic properties, CuNPs demonstrated high antioxidative activity. When the concentration of the nano particles was high (100 μg/ml), the ratio of reactive oxygen species (ROS) was reduced as much as 50%, which in turn suggested antioxidant activity. There was plenty of evidence that CuNPs had anti-cancer potential; this has been shown by the effect of the molecules on the PI3K/AKT/mTOR pathway, which was one of the pathways crucial for cancer survival. Western blot analysis and qRT-PCR results indicated a widespread degradation of the proteins in this pathway upon CuNP exposure. Interestingly, there was a declined phosphorylation up to 75% of PI3K, AKT, and mTOR at 100 μg/ml (p<0. 001). In summary, these findings illustrated the mechanisms behind the therapeutic effect of CuNPs, thus making them good targets for the NSCLC treatment. CuNPs have cytotoxic and antioxidant capacity, as well as significant alterations in lung cancers pathway, and therefore they can be considered as anti-cancer candidates.

摘要

这项研究确立了用茴香提取物制备的铜纳米颗粒(CuNPs)的细胞毒性、抗氧化和抗癌作用,尤其对非小细胞肺癌(NSCLC)也有作用。CuNPs对两种NSCLC细胞系A549和H1650呈剂量依赖性细胞毒性。在100μg/ml时,CuNPs使A549细胞的细胞活力降低至70%,使H1650细胞的细胞活力降低至65%,显示出细胞毒性作用(p<0.05)。测试表明,细胞中相应存在高比例的乳酸脱氢酶(LDH)。除了细胞毒性外,CuNPs还表现出高抗氧化活性。当纳米颗粒浓度较高(100μg/ml)时,活性氧(ROS)比例降低多达50%,这反过来表明具有抗氧化活性。有大量证据表明CuNPs具有抗癌潜力;分子对PI3K/AKT/mTOR通路的作用已证明了这一点,该通路是癌症存活的关键通路之一。蛋白质免疫印迹分析和qRT-PCR结果表明,暴露于CuNPs后该通路中的蛋白质广泛降解。有趣的是,在100μg/ml时,PI3K、AKT和mTOR的磷酸化下降高达75%(p<0.001)。总之,这些发现阐明了CuNPs治疗作用背后的机制,因此使其成为NSCLC治疗的良好靶点。CuNPs具有细胞毒性和抗氧化能力,以及对肺癌通路的显著改变,因此可被视为抗癌候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be7/11717185/23c9a2b38991/pone.0309207.g001.jpg

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