Anti-tumor immune effect of ginseng glucosyl oleanolate transformed from ginsenoside Ro by activating the cGAS/STING pathway and regulating gut microbiota in cervical cancer

Abstract Ginseng (Panax ginseng C.A. Meyer) is a natural immune modulator with a long history of application. Ginsenosides, especially rare ginsenosides, as main bioactive components, have received extensive attention for modulating immune response in cancers. This study aimed to investigate the anti-tumor immune effect of the new rare ginseng glucosyl oleanolate (GGO) transformed from ginsenoside Ro in cervical cancer. GGO effectively induced cervical cancer cell apoptosis, inhibited epithelial mesenchymal transformation (EMT) and tumor growth in dose manner. GGO inhibited immune escape, increased the infiltration of immune cells cluster of differentiation 4 (CD4) T cells and cluster of differentiation 8 (CD8) T cells and the secretion of cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) by activating the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) signaling pathway. In addition, GGO enhanced short-chain fatty acids (SCFAs) metabolism and intestinal immune barrier function by modulating the composition of gut microbiota through specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Blautia, among others, and these influences also contributed to its anti-tumor immune effect. The results of this study offered encouraging indications that GGO might serve as a natural functional food ingredient with the potential to prevent and treat cervical cancer.