Journal of Southern Medical University

Journal of Southern Medical University ›› 2021, Vol. 41 ›› Issue (12): 1763-1772.doi: 10.12122/j.issn.1673-4254.2021.12.02

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Therapeutic mechanism of natural astaxanthin against renal clear cell carcinoma based on network pharmacology and bioinformatics

GAO Junjie, YANG Dandan, CAO Ruoxue, PAN Xueshan, XIA Jun   

  1. Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, China; Department of Laboratory Medicine, Second People's Hospital of Lianyungang, Lianyungang 222000, China
  • Online:2021-12-20 Published:2022-01-04

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Abstract: 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 (P<0.001) in correlation with a poor prognosis (HR=1.37, P=0.043). Molecular docking showed that the binding energy of AST and PGF was -5.43 kcal/mol. CCK-8 assay showed that AST at the concentration of 50 μmol/L was capable of inhibiting the proliferation of KIRC cells, and a higher concentration resulted in a stronger inhibitory effect. The results of RT-qPCR and Western blotting showed that AST treatment significantly reduced the expression of PGF at both the mRNA and protein levels in KIRC cells. Conclusion Natural AST can suppress the proliferation of KIRC and inhibit the expression of PGF in the cells.

Key words: network pharmacology; bioinformatics; natural astaxanthin; renal clear cell carcinoma; placental growth factor