Diosmetin 与 Chrysin 通过抑制 PI3K/AKT/mTOR/NF-кB 信号通路联合对抗肝细胞癌:TCGA 分析、分子对接、分子动力学、体外实验。

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiang Yu, Di Zhang, Chengming Hu, Zejun Yu, Yang Li, Cheng Fang, Yinsheng Qiu, Zhinan Mei, Lingyun Xu
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引用次数: 0

摘要

肝细胞癌(HCC)是发病率第六高的恶性肿瘤。肝细胞癌的发生与细胞凋亡、自噬和炎症密切相关。Diosmetin 和 Chrysin 是两种黄酮类化合物,具有抗炎和抗癌特性。本研究利用 TCGA 数据库确定正常人和 HCC 患者之间的差异表达基因。利用分子对接和分子动力学分析评估了菊黄素和香叶木素与 PI3K/AKT/mTOR/NF-κB 信号通路中关键蛋白的结合亲和力。研究采用了 Western 印迹法和 RT-qPCR 法测量该通路中的蛋白质和基因表达。结果表明,与正常人相比,HCC 患者的 PI3K、AKT、mTOR 和 P65 蛋白水平升高,这对患者的生存产生了不利影响。分子对接和动力学研究表明,香叶木素和金丝桃素能有效地与这四种蛋白结合。体外实验显示,地奥司明和金丝桃素的组合可通过抑制PI3K/AKT/mTOR/NF-κB信号通路,诱导细胞凋亡、增强自噬、减少炎症介质的产生并改善肿瘤细胞微环境。值得注意的是,香叶木素(25 μM)和金丝桃素(10 μM)组合的协同作用得分是 16。因此,由于其强大的协同作用,二osmetin-菊粉组合有望成为治疗肝细胞癌的有效方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combination of Diosmetin With Chrysin Against Hepatocellular Carcinoma Through Inhibiting PI3K/AKT/mTOR/NF-кB Signaling Pathway: TCGA Analysis, Molecular Docking, Molecular Dynamics, In Vitro Experiment

Hepatocellular carcinoma (HCC) is the sixth most prevalent malignant tumor. Hepatocellular carcinogenesis is closely linked to apoptosis, autophagy, and inflammation. Diosmetin and chrysin, are two flavonoid compounds, exhibit anti-inflammatory and anticancer properties. In this study, the TCGA database was utilized to identify differentially expressed genes between normal subjects and HCC patients. Molecular docking and molecular dynamics analyses were employed to assess the binding affinity of chrysin and diosmetin to key proteins in the PI3K/AKT/mTOR/NF-κB signaling pathway. Western blotting and RT-qPCR were used to measure the protein and gene expression within this pathway. The results indicated that HCC patients had elevated levels of PI3K, AKT, mTOR, and P65 proteins compared to normal subjects, which adversely affected patient survival. Molecular docking and dynamics studies demonstrated that diosmetin and chrysin are effectively bound to these four proteins. In vitro experiments revealed that the combination of diosmetin and chrysin could induce apoptosis, enhance autophagy, reduce inflammatory mediator production, and improve the tumor cell microenvironment by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. Notably, the synergy score for the combination of diosmetin (25 μM) and chrysin (10 μM) was 16. Thus, the diosmetin–chrysin combination shows promise as an effective therapeutic approach for hepatocellular carcinoma due to its strong synergistic effect.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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