Exploring the effect and mechanism of fucoidan on liver cancer depending on network pharmacology and experimental verification

Xinghua Li¹Chengyu Yang¹Liwei Wang²Ihsan Ullah³Liu Xinyue⁴Chunqi Feng⁵Qi Liu^1*

• ¹College of Life Sciences, ShanxiUniversity, Taiyuan, China
• ²Shanxi Cancer Hospital, Taiyuan, China
• ³School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
• ⁴Changzhi People's Hospital, Changzhi, China
• ⁵School of Pharmacy, Shanxi Medical University, Taiyuan, China

Objective: This research investigates the anti-liver cancer mechanisms of fucoidan by integrating network pharmacology analysis, molecular docking, and in vitro validation.Methods: 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.Results: 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. In vitro 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. Conclusion: 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.