Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.

ABSTRACT: Metformin is a widely used antidiabetic drug for cancer prevention and treatment. However, the overproduction of lactic acid and its inefficiency in cancer therapy limit its application. Here, we demonstrate the synergistic effects of the lactate/GPR81 blockade (3-hydroxy-butyrate, 3-OBA) and metformin on inhibiting cancer cells growth in vitro. Simultaneously, this combination could inhibit glycolysis and OXPHOS metabolism, as well as inhibiting tumor growth and reducing serum lactate levels in tumor-bearing mice. Interestingly, we observed that this combination could enhance the functions of Jurkat cells in vitro and CD8⁺ T cells in vivo. In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blo

SUBMITTER: Chen S 

PROVIDER: S-EPMC8466555 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature