Lastly, Metformin was shown to suppress HO-1 mRNA and protein expression in human HCC HepG2, cervical cancer HeLa, and NSCLC A549 cells, markedly reducing NRF2 mRNA and protein levels by inactivating RAF/ERK signaling [356] (see Table 2). This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.