Ginsenoside Rb1 inhibits chronic stress-induced colorectal cancer via regulating glycolysis and β2-AR/CREB1 signaling pathway

To investigate the mechanism of ginsenoside Rb1 (G-Rb1) against colorectal cancer under chronic stress. A chronic restraint stress (CRS) model and a colorectal cancer (CRC) subcutaneous xenograft model were established. Western blot analysis quantified β2-adrenergic receptor (β2-AR), cAMP response element-binding protein 1 (CREB1), and p-CREB1 expression. Additionally, glycolytic enzymes GLUT1, HK2, and PFKP were analyzed via Western blot and RT-qPCR, with glucose uptake, lactate, ATP, and stress hormone levels assessed by flow cytometry, kits, and ELISA. Compared to the control group, the stress group exhibited increased tumor volume and mass, along with elevated expression of β2-AR, p-CREB1, and upregulated expression levels of GLUT1, HK2, and PFKP. Additionally, glucose, lactate, and epinephrine levels were higher in the stress group. In comparison to the stress group, G-Rb1 treatment demonstrated reduced tumor volume and mass, decreased p-CREB1 expression, as well as downregulated protein and mRNA levels of GLUT1, HK2, and PFKP. Glucose, lactate, and epinephrine levels also showed a reduction in the G-Rb1-treated groups. G-Rb1 suppresses the growth of colorectal cancer under chronic stress, potentially through downregulation of the β2-AR/CREB1 signaling pathway, thereby reducing glycolytic activity in colorectal cancer under chronic stress.