Besides, Nrf2 can effect the heme-binding ferrous content by regulating intracellular heme synthesis and metabolism [34].These results indicated that metformin induced ferroptosis of lung cancer cells through Nrf2/HO-1 signaling axis, yet the specific mechanism through which metformin regulates the Nrf2/HO-1 signaling pathway and ferroptosis in lung cancer is unclear, and whether the activation or silencing of genes of Nrf2/HO-1 signaling pathway could change the metformin-induced ferroptosis remains to be further studied. This evidence concerns the gene NFE2L2 and lung cancer.