The Anti-Tumor Effect and Mechanism of Triterpenoids in Mill. on Reversing Effector CD8+ T-cells Dysfunction by Targeting Glycolysis Pathways in Colorectal Cancer

Abstract

Rhus chinensis Mill. is a traditional Chinese medicine (TCM) which is commonly used for cancer treatments. Our previous work had proven that triterpenoids of Rhus chinensis (TER) could effectively regulate glycolysis involved in colorectal cancer (CRC) and play an important role in the prevention of T-cells dysfunction. This study aimed to systematically investigate the effects and mechanisms of TER on glucose metabolism in CRC, while the regulatory mechanisms of TER on restoring T-cells function and activity in CRC were explored as well. The extract of triterpenoids from Rhus chinensis was obtained, and production of lactic acid and glucose uptake were assayed. Also, the expression of CD8+ T-cells surface markers, cytokines secreted by CD8+ T cells, and the expression of key glycolytic enzymes and glucose deprivation induced by tumor cells were further examined. Notably, results showed that TER prevented the dysfunction in CD8+ T cells by enhancing mTOR activity and subsequent cellular metabolism. Furthermore, our findings also demonstrated that TER promoted glycolytic gene expression in CD8+ T cells in vivo, and significantly inhibited tumor growth. Altogether, our studies suggested that TER not only reversed effector CD8+ T-cells dysfunction and enhanced T-cells recognition, but also improved tumor microenvironment, thereby providing new insight into the prevention and treatment of CRC with TCM.