What question did this study set out to answer?

This study aims to explore the anti-cancer effects of Morusin on esophageal cancer and elucidate its mechanisms using various analytical approaches.

March 25, 2026Open Access

Integrated analysis of Morusin inhibiting esophageal cancer via network pharmacology molecular dynamics simulation and in vitro validation

Key Points

This study aims to explore the anti-cancer effects of Morusin on esophageal cancer and elucidate its mechanisms using various analytical approaches.
Employed network pharmacology to identify therapeutic targets of Morusin.
Conducted molecular dynamics simulations to assess Morusin interactions with proteins.
Performed in vitro experiments to evaluate the effects of Morusin on esophageal cancer cells.
Analyzed gene expression data and created a protein–protein interaction network.
Executed Western blot analysis to assess apoptosis and signaling pathways.
Identified 21 common therapeutic targets for Morusin in esophageal cancer.
Morusin significantly inhibited cell proliferation in EC cells (KYSE150 and TE1) at 10 µM concentration.
Demonstrated that Morusin suppressed EC cell migration and invasion.
Western blot results showed increased apoptosis markers and decreased MAPK pathway activity.

Abstract

Esophageal cancer (EC) is a malignant tumor characterized by high incidence and mortality, and its complex pathogenesis necessitates the development of effective therapeutic strategies. In this study, we investigated the anti-cancer effects and underlying mechanisms of Morusin against EC using network pharmacology, molecular dynamics (MD) simulation, and in vitro experiments. Transcriptomic analysis identified 3,540 differentially expressed genes in EC as potential therapeutic targets, while potential targets of Morusin were predicted using the SWISSprediction database. The intersection analysis revealed 21 common genes, which may represent the key targets of Morusin in EC treatment. A protein–protein interaction (PPI) network was constructed using the STRING database and analyzed in Cytoscape 3.8.0, identifying MAPK3, PTGS2, and HSP90AA1 as core hub genes. GO enrichment analysis indicated that the biological processes involved in Morusin’s anti-EC activity mainly included peptidyl-serine phosphorylation, peptidyl-serine modification, and aging. The cellular components were primarily associated with focal adhesion, cell–substrate junction, and caveola, while the molecular functions were enriched in protein serine kinase activity, protein serine/threonine kinase activity, protein serine/threonine/tyrosine kinase activity, and MAP kinase kinase activity. KEGG pathway enrichment suggested that Morusin may exert its effects through the HIF-1 signaling pathway, prostate cancer, and serotonergic synapse pathways. Molecular docking and MD simulations demonstrated stable binding of Morusin to ERK1 (MAPK3) and MEK1. In vitro assays revealed that 10 µM Morusin markedly inhibited the proliferation of EC cells (KYSE150 and TE1) without significant cytotoxicity toward normal esophageal epithelial cells (Het-1 A). Furthermore, Transwell and wound-healing assays confirmed that Morusin suppressed EC cell migration and invasion. Western blot analysis showed that Morusin treatment decreased Bcl-2 expression and increased cleaved-caspase3/caspase3, cleaved-PARP/PARP, and Bax levels, accompanied by significant downregulation of p-MEK1/2, p-MAPK3, and p-ERK2. Collectively, these findings suggest that Morusin inhibits proliferation, migration, and invasion, and induces apoptosis in EC cells by suppressing the MAPK signaling pathway.

Bookmark

View Full Paper

Cite This Study

Yang et al. (Mon,) studied this question.

synapsesocial.com/papers/69c37b11b34aaaeb1a67d2e6 https://doi.org/https://doi.org/10.1007/s12672-026-04839-y

Bookmark

View Full Paper