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

Abstract

Objective: To investigate the mechanism of ginsenoside Rb1 (G-Rb1) against colorectal cancer under chronic stress.

Methods: 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.

Key findings: 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.

Conclusions: 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.