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由马尾藻多糖稳定的线粒体靶向硒纳米颗粒增强活性氧介导的抗肿瘤活性。

Mitochondrion-targeted selenium nanoparticles stabilized by Sargassum fusiforme polysaccharides increase reactive oxygen species-mediated antitumour activity.

作者信息

Chen Yanzhe, Zhu Feifei, Ou Jieying, Chen Jianping, Liu Xiaofei, Li Rui, Wang Zhuo, Cheong Kit-Leong, Zhong Saiyi

机构信息

College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China; Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Zhanjiang, China; Guangdong Provincial Engineering Technology Research Center of Seafood, Zhanjiang, China; Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang, China; Guangdong Provincial Modern Agricultural Science and Technology Innovation Center for Subtropical Fruit and Vegetable Processing, Zhanjiang, China.

College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China; Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Zhanjiang, China; Guangdong Provincial Engineering Technology Research Center of Seafood, Zhanjiang, China; Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang, China; Guangdong Provincial Modern Agricultural Science and Technology Innovation Center for Subtropical Fruit and Vegetable Processing, Zhanjiang, China.

出版信息

Int J Biol Macromol. 2024 Nov;281(Pt 4):136545. doi: 10.1016/j.ijbiomac.2024.136545. Epub 2024 Oct 12.

Abstract

Authors prepared a nanoselenium particle stabilized with Sargassum fusiforme polysaccharide (SFPS-Tw-SeNPs) and confirmed that it could effectively inhibit the proliferation of A549 lung cancer cells in vitro. The aim of this study was to investigate its anti-lung cancer effect in vitro and in vivo and its possible mechanism. In cell experiments, AO/EB staining revealed that SFPS-Tw-SeNPs could induce the apoptosis of A549 cells and produce red fluorescence by inserting into DNA through damaged cell membranes, increasing the production of reactive oxygen species (ROS). SFPS-Tw-SeNPs that is loaded with coumarin-6 entered the cells in a concentration-dependent and time-dependent manner, acting on the mitochondria, reducing the mitochondrial membrane potential, increasing the Bax/Bcl-2 ratio, and increasing the expression of Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP and Cytochrome C-induced apoptosis in cells. In addition, the SFPS-Tw-SeNPs blocked the PI3K/AKT signalling pathway, downregulated the expression of Cyclin-A and CDK2, upregulated the expression of P21, and arrested the cell in the G1 phase. In animal experiments, SFPS-Tw-SeNPs treatment significantly inhibited the growth of A549 tumour xenografts but did not significantly negatively affect the body of the animals. Overall, SFPS-Tw-SeNPs have the potential to be developed as a pharmaceutical drug to prevent and treat non-small cell lung cancer.

摘要

作者制备了一种用羊栖菜多糖稳定的纳米硒颗粒(SFPS-Tw-SeNPs),并证实其在体外能有效抑制A549肺癌细胞的增殖。本研究的目的是探讨其在体外和体内的抗肺癌作用及其可能的机制。在细胞实验中,AO/EB染色显示SFPS-Tw-SeNPs可诱导A549细胞凋亡,并通过受损细胞膜插入DNA产生红色荧光,增加活性氧(ROS)的产生。负载香豆素-6的SFPS-Tw-SeNPs以浓度和时间依赖性方式进入细胞,作用于线粒体,降低线粒体膜电位,增加Bax/Bcl-2比值,并增加Cleaved-Caspase 3、Cleaved-Caspase 9、Cleaved-PARP和细胞色素C的表达,诱导细胞凋亡。此外,SFPS-Tw-SeNPs阻断PI3K/AKT信号通路,下调Cyclin-A和CDK2的表达,上调P21的表达,并使细胞停滞在G1期。在动物实验中,SFPS-Tw-SeNPs治疗显著抑制了A549肿瘤异种移植瘤的生长,但对动物身体没有显著的负面影响。总体而言,SFPS-Tw-SeNPs有潜力被开发为预防和治疗非小细胞肺癌的药物。

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