PSY Suppresses Colorectal Cancer Progression by Targeting Oncogenic Signaling and Metabolic Reprogramming

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by dysregulated oncogenic signaling and metabolic reprogramming. PSY, an herbal formula derived from Patriniae Radix, Coix Seed, and Mori Cortex Radicis, has shown potential anti-cancer effects, but its mechanisms in CRC remain unclear. Purpose: PSY's multi-targeted effects on oncogenic signaling, metabolic pathways, and inflammation in CRC. Materials and Methods: Transcriptomic profiling (RNA sequencing), in vitro assays, and in vivo xenograft models were used to elucidate PSY's mechanisms. Metabolic profiling via LC-MS/MS and serum lipid analysis were performed to assess its impact on lipid metabolism. Results: PSY activated the PERK/eIF2a/ATF4 stress pathway and suppressed PI3K/Akt/mTOR signaling, inducing apoptosis and inhibiting CRC cell proliferation. Xenograft models showed significant tumor growth suppression and reduced proliferation (Ki67) and inflammation markers (COX2, p-STAT3). Metabolic profiling revealed reduced cholesterol and fatty acid biosynthesis, including arachidonic acid, correlating with COX2 downregulation. Serum LDL and HDL levels decreased, with an increased LDL/HDL ratio. Conclusion: PSY demonstrates potential as a multi-targeted agent by disrupting oncogenic signaling, lipid metabolism, and inflammation in CRC. These findings support its further exploration for clinical applications. Overall design: RNA-seq was conducted to identify transcriptomic changes in HCT116 colorectal cancer cells treated with PSY for 24 hours, compared to DMSO control.