OBJECTIVE: To explore the molecular mechanism by which natural astaxanthin (AST) inhibits renal clear cell carcinoma (KIRC) based on network pharmacology and bioinformatics.
METHODS: PharmMapper database was used to retrieve the targets of natural astaxanthin, and TCGA database was used to identify the differentially expressed genes (DEGs) in KIRC and adjacent tissues. The target genes of AST was analyzed using Cytoscape software to construct the “drug-target” network diagram. The visual protein-protein interaction (PPI) network was constructed using String database, and GO enrichment analysis of the core targets was performed. Single gene bioinformatics was performed to verify the screened core target of AST, namely placental growth factor (PGF). The effect of natural AST on the viability of KIRC cells was tested using CCK-8 method, and the binding between natural AST and PGF was assessed with molecular docking technology. The effect of natural AST on the mRNA and protein expression of the target genes was analyzed using RT-qPCR and Western blotting.
RESULTS: We identified 278 candidate targets of AST, 1081 KIRC-related targets, and 7 core targets involved in the therapeutic mechanism of AST against KIRC. Among these 7 core targets, PGF showed significantly upregulated expression in KIRC (
CONCLUSION: Natural AST can suppress the proliferation of KIRC and inhibit the expression of PGF in the cells.