Ginseng bioactive compounds reverse rectal cancer therapy resistance by targeting CYP26A1 and modulating B-Cell mediated immunity

This study explores how ginseng bioactive compounds overcome radio- and chemoresistance in rectal cancer by targeting CYP26A1 and modulating immunity. Bioinformatic analyses identified CYP26A1 as a critical resistance-related gene associated with poor prognosis and reduced B-cell infiltration. Molecular docking revealed strong binding between CYP26A1 and five ginseng components (Aposiopolamine, Celabenzine, Frutinone A, Girinimbin, and Inermin). In vitro experiments further confirmed that ginseng extract inhibited the proliferation of colorectal cancer cells, induced apoptosis, caused cell-cycle arrest, and suppressed cell migration and invasion. In addition, ginseng extract enhanced B-cell activity and promoted the secretion of granzyme B, IFN-γ, and TNF-α, thereby modulating the immune microenvironment and ultimately influencing tumor cell sensitivity to radiotherapy and chemotherapy. Collectively, these findings suggest that ginseng bioactives may reverse treatment resistance through CYP26A1 inhibition and immune modulation, highlighting their potential as adjuvants to improve therapeutic response in rectal cancer. This study identifies for the first time that active components of ginseng may reverse RCR in RC by inhibiting CYP26A1, which promotes the accumulation of B-cells, memory B-cells, and naive B-cells in RC tissue.CYP26A1 expression is upregulated in RT/CT-resistant samples and tumor tissues, and it is positively correlated with poor patient prognosis.A LASSO risk regression model constructed based on the expression of CCDC85A, CYP26A1, HOXD1, MYLK, and NCCRP1 in TCGA-READ data offers valuable guidance for prognostic evaluation in RC patients.Molecular docking and MD simulations suggest that ginseng active compounds have a potential binding affinity for CYP26A1.This study proposes a potential “CYP26A1–immunity–ginseng components” mechanism, although the conclusions require further validation through in vivo experiments and clinical studies. This study identifies for the first time that active components of ginseng may reverse RCR in RC by inhibiting CYP26A1, which promotes the accumulation of B-cells, memory B-cells, and naive B-cells in RC tissue. CYP26A1 expression is upregulated in RT/CT-resistant samples and tumor tissues, and it is positively correlated with poor patient prognosis. A LASSO risk regression model constructed based on the expression of CCDC85A, CYP26A1, HOXD1, MYLK, and NCCRP1 in TCGA-READ data offers valuable guidance for prognostic evaluation in RC patients. Molecular docking and MD simulations suggest that ginseng active compounds have a potential binding affinity for CYP26A1. This study proposes a potential “CYP26A1–immunity–ginseng components” mechanism, although the conclusions require further validation through in vivo experiments and clinical studies. Analysis Workflow and Potential Mechanisms of Ginseng Active Components in Reversing RC-RCR.