Therapeutic targets and signaling pathways of active components of QiLing decoction against castration-resistant prostate cancer based on network pharmacology

PeerJ. 2022 Jun 27:10:e13481. doi: 10.7717/peerj.13481. eCollection 2022.

Abstract

QiLing decoction (QLD) is a traditional Chinese medicine compound. This study aims to explore the therapeutic effect of QLD in castration-resistant prostate cancer (CRPC) and its potential bio-targets. A total of 51 active components and QLD 149 targets were identified using bioinformatics analysis. Additionally, five optimal hub target genes were screened including tumor protein P53 (TP53), interleukin-6 (IL-6), vascular endothelial growth factor-A (VEGF-A), caspase-3 (CASP-3), and estrogen receptor-1 (ESR-1). The interrelated network between active components of QLD and their potential targets was constructed. The molecular function, biological processes, and signaling pathways of QLD-against CRPC were identified. Moreover, QLD was found to efficiently exert a repressive effect on CRPC tumor growth mainly by suppressing the activation of HIF-α/VEGFA and TNF-α/IL6 signaling pathways, and increasing the P53 expression level. These results successfully indicated the potential anti-CRPC mechanism of the active components of QLD.

Keywords: Active components; Castration-resistant prostate cancer; Network pharmacology; QiLing decoction; Signaling pathways; Tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Male
  • Network Pharmacology
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Signal Transduction
  • Tumor Suppressor Protein p53* / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was funded by the General Program of the National Natural Science Foundation of China: Study on the mechanism of Qi Ling Decoction’s regulation of JNK/Bcl-2-Beclin1 signal axis via miRNA-143 to inhibit autophagy against Abiraterone resistance in prostate cancer, Subject number: 82174199: Purchase of experimental materials; Shanghai University of Traditional Chinese Medicine Industry Development Center Medical and Nursing Integrated Science and Technology Innovation Project: Study on the mechanism of ”Qi Ling Decoction” delaying castration resistance in prostate cancer based on IL6/STAT3-mediated immune pathway in tumor microenvironment, Subject number: 2069: Equipment leasing; Shanghai Municipal Health Commission special subject of Chinese traditional medicine research: Study on the mechanism of the prescriptions of “Qi Ling” regulating tumor microenvironment and inhibiting CRPC cell proliferation and invasion through IL6/STAT3, Subject number: 2020JQ002 and Shanghai Science and Technology Commission Shanghai Natural Science Foundation Project: Study on mechanism about prescriptions of “Qi Ling” inhibiting androgen-independent transformation of prostate cancer cells by AR signaling pathway based on TRIM66 / HP1 gamma complex, Subject number: 19ZR1458200: Testing and processing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.