Danshensu IIA Inhibits Liver Cancer Progression: Mechanism Based on the MAPK/NF-κB Signaling Pathway

Background Liver cancer (LC) remains a leading cause of cancer-related mortality worldwide, with poor prognosis largely due to tumor heterogeneity, aggressive proliferation, and immune evasion. The MAPK and NF-κB signaling pathways play pivotal roles in promoting tumor growth and resistance to apoptosis. Danshensu IIA, a bioactive component derived from Salvia miltiorrhiza, has demonstrated anti-tumor potential, yet its mechanistic effects on LC remain insufficiently characterized. Methods We integrated single-cell RNA sequencing (scRNA-seq) analysis of LC tissues with functional enrichment and survival analysis to identify candidate pathways and prognostic markers. Key findings were validated by in vitro assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, quantitative PCR, and Western blot analysis of apoptosis-related and signaling proteins. Results scRNA-seq analysis revealed distinct LC cell subpopulations enriched in MAPK and NF-κB signaling components, with high expression correlating with reduced overall survival. Functional enrichment indicated pro-tumor and immunosuppressive phenotypes in specific clusters. In vitro, Danshensu IIA significantly inhibited LC cell proliferation and migration, reduced colony formation, and induced apoptosis, as evidenced by increased Bax, Caspase‑3, Caspase‑9, and P53 levels, and decreased Bcl‑2 expression. These effects were accompanied by suppression of MAPK and NF-κB pathway activity, consistent with transcriptomic predictions. Conclusion Danshensu IIA exerts potent anti-tumor effects in LC by targeting MAPK and NF-κB signaling, leading to reduced proliferation, impaired migration, and enhanced apoptosis. This combined bioinformatics–experimental approach highlights Danshensu IIA as a promising therapeutic candidate for LC treatment.