Li Xinghua, Yang Chengyu, Wang Liwei, Ullah Ihsan, Liu Xinyue, Feng Chunqi, Liu Qi
College of Life Sciences, Shanxi University, Taiyuan, China.
Institute of Upper Gastrointestinal Tumour Prevention and Treatment, Shanxi Medical University, Changzhi, China.
Front Chem. 2025 Jul 16;13:1638785. doi: 10.3389/fchem.2025.1638785. eCollection 2025.
This research investigates the anti-liver cancer mechanisms of fucoidan by integrating network pharmacology analysis, molecular docking, and validation.
Potential targets of fucoidan were first predicted using the SwissTargetPrediction platform. Subsequently, targets associated with liver cancer were identified through data extraction from three established databases: GeneCards, OMIM, and TTD, and the intersection between the targets of fucoidan and liver cancer was identified. A network integrating disease-associated and drug-target interactions was established by analyzing overlapping targets, and the core targets for fucoidan's anti-liver cancer effect were identified through topological network analysis. Functional enrichment analyses, including Gene Ontology (GO) annotation and KEGG pathway analysis, were performed via the Hiplot platform. Molecular docking of the core targets with fucoidan was conducted using AutoDock to asses binding affinities. Finally, experimental validation was performed using real-time PCR and Western blotting to examine the effects of fucoidan on target proteins and signaling pathways.
A total of 69 common targets and 10 core targets were identified. These target genes were primarily involved in regulating biological processes such as cell apoptosis and proliferation, and were significantly associated with the PI3K/Akt and MAPK signaling pathways. Molecular docking demonstrated favorable binding affinities between fucoidan and the core target proteins. experiments revealed that fucoidan significantly inhibited the proliferation of HepG2 cells, downregulated the mRNA expression levels of AKT1, PI3K, PIK3R1, and PIK3CA, and reduced the protein expression of PI3K and Akt in the PI3K/Akt, indicating effective inhibition of the PI3K/Akt signaling pathway.
Fucoidan exerts its anti-liver cancer effect primarily by downregulating mRNA expression levels of target genes including AKT1, PI3K, PIK3R1, PIK3CA and other targets, inhibition of PI3K/Akt signaling pathway activation, and suppressing HepG2 cell proliferation.
本研究通过整合网络药理学分析、分子对接和验证，探讨岩藻依聚糖的抗肝癌机制。
首先使用瑞士靶点预测平台预测岩藻依聚糖的潜在靶点。随后，通过从三个已建立的数据库（基因卡片、在线人类孟德尔遗传数据库和治疗靶点数据库）中提取数据，确定与肝癌相关的靶点，并找出岩藻依聚糖靶点与肝癌靶点的交集。通过分析重叠靶点建立一个整合疾病相关和药物 - 靶点相互作用的网络，并通过拓扑网络分析确定岩藻依聚糖抗肝癌作用的核心靶点。通过Hiplot平台进行功能富集分析，包括基因本体（GO）注释和京都基因与基因组百科全书（KEGG）通路分析。使用自动对接软件对核心靶点与岩藻依聚糖进行分子对接，以评估结合亲和力。最后，通过实时聚合酶链反应（PCR）和蛋白质免疫印迹法进行实验验证，以检测岩藻依聚糖对靶蛋白和信号通路的影响。
共鉴定出69个共同靶点和10个核心靶点。这些靶基因主要参与调节细胞凋亡和增殖等生物学过程，并与PI3K/Akt和丝裂原活化蛋白激酶（MAPK）信号通路显著相关。分子对接表明岩藻依聚糖与核心靶蛋白之间具有良好的结合亲和力。实验表明，岩藻依聚糖显著抑制肝癌细胞系HepG2细胞的增殖，下调AKT1、PI3K、PIK3R1和PIK3CA的mRNA表达水平，并降低PI3K/Akt信号通路中PI3K和Akt的蛋白表达，表明对PI3K/Akt信号通路有有效抑制作用。
岩藻依聚糖主要通过下调包括AKT1、PI3K、PIK3R1、PIK3CA等靶基因的mRNA表达水平，抑制PI3K/Akt信号通路激活，以及抑制HepG2细胞增殖来发挥其抗肝癌作用。
