Oridonin Suppresses Colorectal Cancer Growth In Vitro and In Vivo: Evidence from Integrated Transcriptomic and Proteomic Profiling

Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, and effective therapeutic options for advanced disease are still limited. Oridonin (ORI), a naturally derived diterpenoid compound, has shown anti-tumor activity in several malignancies, but its molecular mechanisms in CRC remain incompletely understood. In this study, the anti-cancer effects of ORI were evaluated in HT-29 and HCT116 colorectal cancer cells using in vitro assays, integrated transcriptomic and proteomic analyses, Western blotting, and an HT-29 xenograft model. ORI reduced cell viability in a time- and concentration-dependent manner, induced G1-phase cell cycle arrest, increased cell death, and reduced wound closure under the tested in vitro conditions. Integrated omics analyses in HT-29 cells identified extensive alterations in gene and protein expression, with significant enrichment of pathways related to cell cycle regulation and apoptosis. Western blotting further showed that ORI increased the expression of BAX, BID, CYCS, and CASP3 while decreasing BCL2 expression. In vivo, ORI significantly inhibited tumor growth in nude mice bearing HT-29 xenografts. These findings indicate that ORI suppresses CRC growth through coordinated regulation of cell cycle progression and apoptosis and suggest that ORI may serve as a potential therapeutic candidate for colorectal cancer.