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image of Melittin Inhibits Ovarian Cancer Cell Growth by Downregulating MMP9 Expression via the JAK2-STAT3 Signaling Pathway

Abstract

Objective

This study aimed to investigate the target sites, core pathways, and mechanisms of action of melittin in treating ovarian cancer through network pharmacology, molecular docking, and experimental verification.

Methods

Potential targets for melittin in ovarian cancer treatment were predicted using databases, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding of the drug to these targets was confirmed through molecular docking. The core targets and pathways were experimentally validated. A tumor-bearing nude mouse model was established, with the mice randomly divided into treatment and control groups. The treatment group received 5 mg/kg of melittin by intraperitoneal injection, whereas the control group received saline injections. Changes in mouse weight and tumor volume were monitored, and protein expression in mouse tumor tissues was assessed immunohistochemistry and Western blotting at the end of the experiment.

Results

Fifty-three common targets between melittin and ovarian cancer were identified in the SEA and GeneCards databases. The Protein-Protein Interaction (PPI) analysis highlighted core targets, including MMP9, STAT3, MMP2, STAT6, FURIN, and BRCA1. The GO enrichment results were related mainly to the metabolic processes of collagen degradation, extracellular matrix disassembly, external encapsulating structures, and phospholipase C-activated G-protein-coupled receptor signaling pathways. The KEGG pathway analysis revealed the enrichment of genes related to estrogen signaling, necroptotic apoptosis, the FoxO signaling pathway, microRNAs in cancer, the JAK-STAT signaling pathway, proteoglycans in cancer, and receptor-mediated carcinogenesis. Cell Counting Kit-8 (CCK8) assays, scratch wound healing tests, and Transwell invasion assays demonstrated that melittin significantly inhibited the proliferation, migration, and invasion of ovarian cancer cells. The Western blot results indicated that melittin downregulated the levels of p-JAK2, p-STAT3, and MMP9 in ovarian cancer cells. Molecular docking demonstrated that melittin bound stably to MMP9 and STAT3. The results of animal experiments indicated that melittin suppressed the growth of ovarian tumors in nude mice and significantly downregulated the expression of MMP9, p-JAK2, and p-STAT3 in tumor tissues (<0.05).

Conclusion

Melittin may inhibit the growth of ovarian cancer cells by downregulating MMP9 expression the JAK2-STAT3 signaling pathway, thus exerting a therapeutic effect.

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2025-04-29
2025-09-10

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Melittin Inhibits Ovarian Cancer Cell Growth by Downregulating MMP9 Expression via the JAK2-STAT3 Signaling Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0109298673355946250403071132
/content/journals/cmc/10.2174/0109298673355946250403071132
/content/journals/cmc/10.2174/0109298673355946250403071132
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  • Article Type:     Research Article
Keywords: JAK-STAT signaling pathway ; matrix metalloproteinase 9 (MMP9) ; network pharmacology ; ovarian cancer ; Western blotting ; Melittin

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