Metformin downregulates CXCL1 expression through AMPK activation. Dose-dependent effect of metformin on AMPK phosphorylation in TE-7 cells was detected by western blotting. (B) TCGA data showing CXCL1 expression together with PRKAA1/2, PRKAB1/2, and PRKAA2. (C-F) After treated with metformin and Compound-C or siRNA-AMPK, CXCL1 expression was measured by qRT-PCR and ELISA. (G) Cells were incubated with metformin, Compound C or siRNA-AMPK, the activity of pAMPK and NF-κB were measured by western blotting. (H) Treatment with Compound-C and si-AMPK reversed the inhibition of PMN-MDSC migration by metformin, shown in a migration assay. And si-AMPK1 or si-AMPK2 alone did not have significantly inhibitory effects on PMN-MDSCs migration compared with si-NC (P = 0.1278 and P = 0.1136 respectively). *P < 0.05; **P < 0.01.