Large-Scale Transcriptome Profiling and Network Pharmacology Analysis Reveal the Multi-Target Inhibitory Mechanism of...

Area of Science:

• Integrative oncology and molecular pharmacology.
• Traditional Chinese Medicine (TCM) and modern cancer research.

Background:

• Prostate cancer (PCa) remains a leading cause of male cancer mortality with limited effective treatments.
• Modified Guizhi Fuling Decoction (MGFD) is a TCM formula used clinically for various tumors.
• Understanding MGFD's mechanisms of action (MOA) against PCa is crucial for therapeutic development.

Purpose of the Study:

• To investigate the anti-cancer effects of MGFD on prostate cancer cells (PC3 and DU145).
• To elucidate the molecular mechanisms underlying MGFD's efficacy in inhibiting PCa.
• To identify key molecular targets and pathways affected by MGFD treatment.

Main Methods:

• In vitro assays including Cell Counting Kit-8, wound healing, and transwell invasion assays were performed.
• High-throughput sequencing based high-throughput screening (HTS²) was employed to generate gene expression profiles.
• Network pharmacology and molecular docking were utilized to identify targets and bioactive compounds.

Main Results:

• MGFD significantly suppressed proliferation, migration, and invasion of PCa cells.
• HTS² analysis revealed MGFD's impact on TNF signaling, cellular senescence, and FoxO signaling pathways.
• Key targets identified include AKT1, CASP8, CDK1, and CCND1, with specific compounds showing strong binding affinities.

Conclusions:

• MGFD exhibits potent anti-prostate cancer effects through multiple molecular mechanisms.
• The multi-target action of MGFD highlights its potential as a novel therapeutic strategy for PCa.
• Further in vivo studies are warranted to validate these promising findings.