Mechanistic investigation of Corydalis yanhusuo in prostate cancer: Targeting the miR-192-5p-PI3K/AKT/mTOR and STAT3-HSP90 pathways.

Prostate cancer remains a major cause of cancer-related mortality, with therapeutic resistance frequently driven by aberrant oncogenic signaling and epithelial-mesenchymal transition (EMT). MicroRNAs (miRNAs), such as miR-192-5p, have emerged as important regulators of tumor progression and drug resistance. Corydalis yanhusuo (CDY), a traditional medicinal herb widely used in East Asia, exhibits a range of pharmacological properties, but its molecular mechanisms of action in prostate cancer are not yet fully defined. In this study, we integrated phytochemical profiling, high-performance liquid chromatography / Liquid chromatography-mass spectrometry (HPLC/LC-MS), in silico molecular docking, network pharmacology, and in vitro and semi-in vivo functional assays to investigate the anti-cancer effects of CDY. Major bioactive compounds, including quercetin, corydaline, and dehydrocorydaline were identified, showing high binding affinity to key oncogenic proteins such as Epidermal growth factor receptor (EGFR), Protein Kinase B (AKT), Phosphoinositide 3-kinase (PI3K), Signal transducer and activator of transcription 3 (STAT3), and Heat shock protein 90 (HSP90). CDY significantly suppressed colony formation and cell migration in DU145 and PC-3 prostate cancer cells, reversed EMT phenotypes by reducing lamellipodia formation and restoring epithelial morphology, and regulated EMT-associated markers. Western blot analysis demonstrated inhibition of EGFR/PI3K/AKT/mTOR (mechanistic Target of Rapamycin) and STAT3/HSP90 signaling, along with marked downregulation of PI3K and phosphorylation levels of EGFR, AKT, and STAT3. CDY also upregulated miR-192-5p expression, which correlated with suppression of EMT-related transcription factors. In the chick chorioallantoic membrane (CAM) assay, CDY inhibited tumor growth and angiogenesis, with enhanced effects in PC-3 cells. These findings suggest that CDY exerts multi-targeted anti-cancer effects by modulating oncogenic signaling pathways and epigenetic regulators, supporting its potential as a promising bioactive lead for prostate cancer. Collectively, these findings demonstrate that CDY exerts mechanistically coordinated anticancer effects in vitro and in chorioallantoic membrane (CAM) models, warranting further validation in mammalian in vivo systems to assess translational relevance.