Research Paper Volume 16, Issue 6 pp 5387—5411
Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer
- 1 Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
- 2 Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
- 3 The First Medicine College, Taizhou Campus of Nanjing University of Traditional Chinese Medicine, Taizhou 225300, China
- 4 Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- 5 Department of Oncology, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian 223812, China
- 6 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Received: August 3, 2023 Accepted: February 20, 2024 Published: March 13, 2024
https://doi.org/10.18632/aging.205654How to Cite
Copyright: © 2024 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. In vitro experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. In vitro, CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.