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氧化铁、海藻酸钠和丁香酚的纳米复合材料通过 PI3K/Akt/mTOR 信号通路诱导 Hep3 细胞凋亡,并在斑马鱼模型中产生肝毒性。

Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model.

机构信息

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.

Department of Surgery, College of Medicine, Majmaah University, P. O. Box 66, Al-Majmaah 11952, Riyadh, Saudi Arabia.

出版信息

Int J Biol Macromol. 2024 Jan;256(Pt 2):127490. doi: 10.1016/j.ijbiomac.2023.127490. Epub 2023 Nov 17.

DOI:10.1016/j.ijbiomac.2023.127490
PMID:37979758
Abstract

Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-FeO-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.

摘要

肝癌是全球最常见的恶性肿瘤之一,也是癌症相关死亡的主要原因之一。由于治疗选择有限,因此迫切需要探索合适的治疗方案。在这方面,纳米技术已被用于探索有前途的化疗方法,特别是用于癌症治疗。纳米技术涉及到药物治疗中纳米粒子的生物学和物理特性。在目前的工作中,使用 SEM 和 TEM、UV-可见、FTIR 和 PL 光谱、XRD、EDAX 和 DLS 研究等多种方法对α-FeO-海藻酸钠-丁香酚纳米复合材料(FSE NCs)进行了配方和表征。NCs 的平均粒径为 50nm,具有菱面体结构。此外,通过细胞活力、双重染色、DCFH-DA、Annexin-V/-FITC/PI、细胞周期分析方法和 PI3K/Akt/mTOR 信号蛋白研究,研究了 NCs 对 Hep3B 肝癌细胞系的抗癌活性,以评估 NCs 在 Hep3B 细胞中的抗癌作用。还使用斑马鱼在体内进行了动物模型的抗癌活性研究,评估了血液学参数、肝酶和组织病理学研究的效果。此外,NCs 降低了细胞活力,增加了 ROS 积累,破坏了膜完整性,减少了抗氧化剂,阻断了细胞周期,并触发了 PI3K/Akt/mTOR 信号通路,最终导致细胞死亡。因此,FSE NCs 具有作为潜在抗癌候选物的巨大潜力。

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