Network Pharmacology and Experimental Validation Identify Paeoniflorin as a Novel SRC-Targeted Therapy for...

Area of Science:

• Oncology
• Pharmacology
• Traditional Chinese Medicine

Background:

• Castration-resistant prostate cancer (CRPC) presents significant treatment challenges due to therapy resistance.
• Traditional Chinese Medicine (TCM) offers potential therapeutic avenues, but the role of paeoniflorin (Pae) in prostate cancer is unexplored.
• Pae is a bioactive compound derived from Paeonia lactiflora.

Purpose of the Study:

• To investigate the therapeutic role and underlying mechanisms of paeoniflorin (Pae) in castration-resistant prostate cancer (CRPC).
• To identify key targets of Pae and develop a prognostic model for CRPC patients.

Main Methods:

• An integrative approach combining network pharmacology, molecular docking, and experimental validation was employed.
• Protein-protein interaction networks and GO/KEGG pathway analyses were performed to identify Pae targets.
• In vitro and in vivo assays, including organoid and xenograft studies, assessed Pae's effects on CRPC cells and tumor growth.

Main Results:

• Pae demonstrated significant anti-CRPC activity, inhibiting cell proliferation by 60% and migration by 65%.
• Pae downregulated SRC proto-oncogene, non-receptor tyrosine kinase (SRC) mRNA expression by 68% and inhibited tumor growth.
• A Pae-target-based prognostic model effectively stratified patients based on survival outcomes.

Conclusions:

• Pae overcomes CRPC resistance by targeting SRC-mediated pathways, offering a novel therapeutic strategy.
• Network pharmacology is a valuable tool for guiding drug discovery in oncology.
• Further clinical investigation of paeoniflorin for precision oncology in CRPC is warranted.