槐定碱衍生物抑制肝癌细胞迁移与侵袭研究

doi:10.16088/j.issn.1001-6600.2024061801

Abstract

Abstract: This study comprehensively applies network pharmacology, bioinformatics, molecular docking, molecular dynamics, transcriptomics, and in vitro experiments to explore the effects and mechanisms of an indole sophoridine derivative containing ester group on the migration and invasion of liver cancer cells. The potential targets of this derivative were retrieved by using PharmMapper, Super-PRED, Swisstarget, and Targetnet databases. Liver cancer metastasis related genes were determined through differential expression analysis. The anti-liver cancer metastasis targets of this derivative were identified by taking intersection between predicted targets of this derivative and liver cancer metastasis related genes. GO/KEGG enrichment analysis was conducted to predict the potential signaling pathways of this derivative. Core targets of this derivative were identified via using protein-protein interaction analysis. Subsequently, molecular docking and molecular dynamics were involved to reveal the potential interaction between this derivative could core target. Furthermore, transcriptome sequencing was performed to obtain differentially expressed genes caused by this derivative. Finally, western blot assays were conducted to validate the effects of this derivative on MAPK pathway. The results showed that this derivative could significantly inhibit the migration and invasion of liver cancer cells. A total of 47 potential liver cancer metastasis related targets were predicted for this derivative, including 5 core targets: STAT3, PPARG, MAP2K1, CDK4, AKT3. The MAPK pathway was significantly enriched in the analysis of predicted genes and differentially expressed genes caused by this derivative. Molecular docking and molecular dynamics simulations also showed that this derivative had a high binding affinity with the core target MAP2K1 (a key node of the MAPK pathway). The results of western blot showed that under this derivative treatment, the core member of the MAPK pathway, p-Erk1/2 protein expression, was downregulated. Conclusion: this indole sophorodine derivative inhibits the migration and invasion of liver cancer cells by reducing the activity of the MAPK/ERK pathway.

Key words: liver cancer, cells migration and invasion, sophoridine derivative 6j, network pharmacology, molecular docking, molecular dynamics, MAPK pathway

CLC Number: R285

WU Lichuan, TAN Zhenkai, QIN Yehao, ZHAO Xuqi, XIE Yuxin, HUANG Liyu, WEI Jinrui. Sophoridine Derivative Against Liver Cancer Cell Migration and Invasion[J].Journal of Guangxi Normal University(Natural Science Edition), 2025, 43(2): 207-220.

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Sophoridine Derivative Against Liver Cancer Cell Migration and Invasion

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