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Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health challenge, underscoring the urgent need for the development of innovative therapeutic approaches. Ranunculus ternatus Thunb., a traditional herb, exhibits potential anticancer properties, but its mechanisms against ESCC remain poorly understood. This study integrates network pharmacology and experimental validation to explore the therapeutic effects of the ethyl acetate extract of Ranunculus ternatus Thunb. (RTE).
Potential targets of RTE and ESCC were screened using public databases. A Protein-Protein Interaction (PPI) network was constructed to identify key targets, followed by GO and KEGG pathway enrichment analyses. The predicted mechanisms were validated using in vitro assays, including cell proliferation analysis and western blot assay in ESCC cell lines.
Network pharmacology analysis identified 274 potential targets, with 14 key genes implicated in the therapeutic effects of RTE. GO analysis revealed significant involvement in the inflammatory response and apoptotic signaling pathways. KEGG pathway analysis highlighted the MAPK, Relaxin, and PI3K/Akt signaling pathways as critical mechanisms. In vitro experiments demonstrated that RTE significantly inhibited the proliferation of EC-109 and TE-13 cells by modulating the MAPK/ERK and PI3K/Akt pathways.
The study reveals that active compounds of RTE target MAPK/ERK and PI3K/Akt pathways, aligning with prior evidence. However, future studies should explore animal models to confirm efficacy.
This study provides a comprehensive understanding of the molecular mechanisms underlying the anticancer effects of RTE against ESCC. These findings underscore the potential of RTE as a promising natural compound for ESCC treatment.