They then co-cultured CAFs and cancer cells to explore metformin’s effect on CAFs and found that 0.2 mM metformin administered for 48 h significantly impairs the stimulatory effect of CAFs by upregulating the Calmodulin-like protein Calml3, thereby inhibiting the proliferation of gastric cancer cells.228 Metformin also downregulates the NF-kB signaling induced by CAFs to inhibit tumor progression.229. Here, NFKB1 is linked to cancer.