Investigating the Anti-Prostate Cancer Mechanism of Yanghe Decoction through the PI3K/AKT/mTOR Signaling Pathway

Advanced prostate cancer is highly metastatic, invasive, and resistant to therapy, leading to poor patient quality of life and high mortality rates. Thus, there is an urgent need for novel and effective treatment strategies. Yanghe Decoction (YHD) is a classic anticancer herbal formula used in the treatment of various cancers. However, its therapeutic effects on prostate cancer and the underlying mechanisms remain unclear.

The active metabolites of YHD were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP), BATMAN-TCM, and SwissTargetPrediction databases. Prostate cancer-related targets were obtained from GeneCards and OMIM, while potential therapeutic targets of Yanghe Decoction for prostate cancer were identified through Gene Ontology (GO) and KEGG enrichment analyses. R programming was employed to elucidate the relationship between prostate cancer-related targets and potential targets of YHD. To further investigate its antiprostate cancer mechanisms, cell proliferation assays using 22RV1 cells and mouse xenograft models were conducted to validate the therapeutic effects and underlying mechanisms. The effects of PI3K/AKT/mTOR signaling on 22RV1 cell proliferation, apoptosis, and cell cycle progression were evaluated using CCK-8 assays, flow cytometry, and Western blot analysis.

Twenty-two active metabolites in YHD were identified through the Traditional Chinese Medicine Systems Pharmacology (TCMSP), BATMAN-TCM, and SwissTargetPrediction databases, corresponding to 1,792 potential targets. The screening criteria included Oral Bioavailability (OB) ≥30% and Drug-Likeness (DL) ≥0.18. GO and KEGG pathway analyses identified the PI3K/Akt/mTOR signaling pathway as a key pathway associated with YHD. Combined in vitro and in vivo experiments demonstrated that YHD significantly inhibits the proliferation of 22RV1 cells. YHD promoted apoptosis in both 22RV1 cells and xenograft tumors, while inhibiting cell cycle progression and invasive capacity. Mechanistically, YHD suppressed the expression of phosphorylated PI3K, AKT, and mTOR proteins.

Yanghe Decoction promoted caspase-3 activity and suppressed Bcl-2 expression. Additionally, it inhibited the phosphorylation of key proteins in the PI3K/AKT/mTOR pathway in a concentration-dependent manner. By inhibiting the PI3K/AKT/mTOR signaling pathway, Yanghe Decoction induced apoptosis in 22RV1 cells, suggesting its potential therapeutic value for prostate cancer. These findings provide novel insights and a promising strategy for the treatment of prostate cancer.

YHD inhibited proliferation and induced apoptosis in prostate cancer 22RV1 cells, potentially through suppression of PI3K/AKT/mTOR signaling pathway activation.