Integrated Computational Chemistry and Experimental Analysis of Fructus Ligustri to Target Chemoresistant Ovarian Cancer Cells

Ovarian cancer remains a leading cause of gynecological cancer mortality due to late diagnosis and limited therapeutic options. Fructus Ligustri Lucidi (FLL), a traditional Chinese medicinal herb, exhibits multiple pharmacological activities, but its anti-ovarian cancer potential remains underexplored. A network pharmacology approach integrating TCMSP, SuperTCM, GeneCards, and STRING databases identified potential FLL bioactives and their ovarian cancer-related targets. Cytoscape and CytoHubba revealed key hub genes. GO and KEGG enrichment analyses were performed to elucidate biological pathways. Molecular docking assessed binding affinities of phytoconstituents with HSP90AA1, SRC, and STAT3. TIMER and GEPIA evaluated gene expression, immune infiltration, and survival relevance. Finally, in vitro analyses, including MTT, Annexin V/PI staining, and Western blotting, validated FLL’s cytotoxic and molecular effects on SKOV3 ovarian cancer cells. Results: Seven active FLL compounds were identified, targeting 162 intersecting genes, including HSP90AA1, SRC, and STAT3. KEGG enrichment highlighted the PI3K-Akt and MAPK signaling pathways. Molecular docking revealed high binding affinities of phytochemicals with hub targets. TIMER analysis indicated that SRC and STAT3 expression correlate with reduced immune infiltration. GEPIA showed upregulation of SRC and STAT3 in tumors and stage-specific expression, though not prognostic. In vitro, FLL reduced SKOV3 viability and induced both early and late apoptosis. Western blotting showed dose-dependent suppression of HSP90AA1 (88% to 12%), SRC (80% to 43%), and STAT3 (66% to 43%) expression. FLL exhibits multi-targeted anti-ovarian cancer effects through modulation of key oncogenic pathways and genes. These findings support its potential as a natural therapeutic agent for ovarian cancer management.