Network Pharmacology and Molecular Docking Strategy Reveal the Mechanism of Tripterygium wilfordii in Treating Castration-Resistant Prostate Cancer

Yang X, Yimamu Y, Xiao W, Jiang S and Pan J

Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, China
Department of Urology, The Sixth Affiliated Hospital, South China University of Technology, China
Department of Urology, The First Affiliated Hospital of Jishou University, China
These authors contributed equally to this work

^*Correspondance to: Jincheng Pan 

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Abstract:

Background: Castration-Resistant Prostate Cancer (CRPC) is an inevitable type of progression in Prostate Cancer (PCa) after Androgen Deprivation Therapy (ADT). Tripterygium wilfordii (TW), a traditional Chinese herbal medicine, is frequently used to treat cancer and other diseases. In order to identify the potential mechanism of TW in the treatment of CRPC, we jointly utilized network pharmacology and molecular docking to perform preliminary investigation and validation. Methods: The active components and corresponding protein targets of TW were screened on TCMSP database, the targets of CRPC were obtained on GeneCards database and DisGeNET database. The intersectional targets of TW and CRPC were obtained on Venn software. Then, we used STRING database to construct a PPI network based on the intersectional targets, further performed GO and KEGG enrichment analyses on the intersectional targets. Finally, molecular docking was approved for the main active components and core targets. In addition, we also carried out immunohistochemical analysis and expression analysis of core targets, which were conducted to determine how TW affects CRPC and what are the most important components, potential targets, and signaling pathways. Results: Our study reveals that kaempferol is the key component of TW treatment for CRPC. The findings of the network pharmacology indicated that TP53, AKT1 and TNF are the potential target genes for TW connected to anti-CRPC actions. Additionally, KEGG analysis revealed that p53 signaling pathway and PI3K-Akt signaling pathway may be the driver of the anti-CRPC impact of TW. The results of molecular docking showed a high affinity between major active components in TW and the key targets in CRPC. Conclusion: This study reveals the potential mechanisms of TW in the treatment of CPRC through multiple targets and signaling pathways and is validated through molecular docking. TW exerts pharmacological effects in CRRC, p53 signaling pathway is of great value. Furthermore, the present study provided a reference for the wide application of TW in clinically managing CRPC.

Keywords:

Tripterygium wilfordii; Castration-Resistant Prostate Cancer; Network pharmacology; Molecular docking

Cite the Article:

Yang X, Yimamu Y, Xiao W, Jiang S, Pan J. Network Pharmacology and Molecular Docking Strategy Reveal the Mechanism of Tripterygium wilfordii in Treating Castration-Resistant Prostate Cancer. Clin Oncol. 2023;8:2011..