Comparative Proteomic Analysis of Drug Shikonin Addition to Liver
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Background: HCC (Hepatocellular Carcinoma) accounts for 85–90% of primary liver cancers and ranks as the third deadliest malignancy worldwide. While targeted therapies have improved outcomes, advanced HCC remains challenging to treat. TCM (Traditional Chinese Medicine), particularly SK (Shikonin) from Lithospermum erythrorhizon , shows promise by targeting multiple cancer hallmarks like apoptosis resistance and angiogenesis. Methods: Using DIA (Data-Independent Acquisition) proteomics, we analyzed SK-treated HCC cell lines. GO (Gene Ontology) enrichment identified key pathways, while molecular docking validated protein interactions. Immunohistochemistry confirmed differential protein expression. Results: SK treatment significantly altered mitochondrial function-related proteins. Nine DEPs (Differentially Expressed Proteins) were consistently regulated across all cell lines, forming a network linked to TP53 and PRKN. Molecular docking supported these interactions, and immunohistochemistry verified DEP expression patterns. Conclusions: SK exerts anti-HCC effects by modulating mitochondrial proteins and key regulators like TP53/PRKN. These findings highlight SK's multi-target potential and support further investigation of TCM compounds for HCC combination therapies.