Uncovering ShuangZi Powder's Anti-Ovarian Cancer Mechanism: A Systems Biology and Experimental Approach.

[OBJECTIVE] This study investigated the anti-ovarian cancer (OC) effects of Shuangzi Powder (SZP) and its regulatory impact on the tumor microenvironment.

[METHOD] This study employed systems biology approaches, integrating molecular docking and experimental validation, to explore the pharmacological mechanisms of SZP in OC treatment. To identify potential bioactive compounds and target genes of SZP, network pharmacology, protein- protein interaction network analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted.

[RESULTS] Among the 11 bioactive ingredients identified in SZP, 1,767 potential therapeutic targets were predicted, while 2,637 differentially expressed genes were found to be associated with OC. KEGG pathway analysis revealed significant enrichment in pathways related to cancer, apoptosis, the PI3K-Akt signaling pathway, and the PD-L1/PD-1 checkpoint pathway. Treatment of A2780 cells with β,β-Dimethylacrylshikonin (DMAS) inhibited cell viability, migration, and invasion. Moreover, DMAS downregulated the expression of cell cycle- and apoptosis-related genes (CCNB1, CHEK1, CCNE1, and PARP1) and upregulated the immune checkpoint gene PD-L1. These findings indicate that multiple components, targets, and pathways are involved in OC treatment by SZP.

[CONCLUSION] DMAS, one of the bioactive ingredients of SZP, was predicted and preliminarily validated to exert inhibitory effects on OC cells, mainly through the regulation of the cell cycle, apoptosis, and immune response, as demonstrated by molecular docking and experimental analyses.