DUXAP8 regulates erastin and sorafenib induced ferroptosis in HCC cells. (A) DUXAP8 knockdown promoted the erastin and sorafenib induced lipid formation (measured by MDA assay) in LM3 (left) and HepaRG (right) cells treated with 10 μM erastin or sorafenib for 24 h. (B) DUXAP8 knockdown increased the GSSG/GSH ratios in erastin or sorafenib treated LM3 (left) and HepaRG (right) cells. (C) DUXAP8 knockdown increased the ROS level (assessed by DCFH‐DA staining) of LM3 cells (two on the left) and HepaRG cells (two on the right) treated with erastin (10 μM) or sorafenib (10 μM) for 24 h. (D) Representative TEM images showing sorafenib‐induced ferroptosis in LM3 cells with and without DUXAP8 knockdown. Scale bar: left, 5 μm; middle, 1 μm; right, 500 nm. (E) DUXAP8 overexpression suppressed the erastin and sorafenib induced lipid formation (measured by MDA assay) in Huh7 (left) and PLC (right) cells treated with 5 μM erastin or 2.5 μM sorafenib for 24 h. (F) DUXAP8 overexpression influenced the intracellular GSSG/GSH ratios in erastin or sorafenib treated Huh7 (left) and PLC (right) cells. (G) DUXAP8 overexpression inhibited the ROS level (assessed by DCFH‐DA staining) of Huh7 (two on the left) and PLC (two on the right) cells treated with erastin (5 μM) or sorafenib (2.5 μM) for 24 h. * p < 0.05, ** p < 0.01, *** p < 0.001. Results represent the average from three independent experiments. sh‐DUX, sh‐DUXAP8; EV, Empty vector; OE, pcDNA DUXAP8; sh‐SLC, sh‐SLC7A11; OE‐SLC, pcDNA SLC7A11.