To assess the roles caspase-3, PARP-1, PERK, and autophagosome play in HCC cells treated with Dox plus Crizo, we further treated HCC cells with inhibitor for PERK, caspase-3 (C3-I), PARP-1, or lysosome respectively in the presence of Dox plus Crizo, we observe significantly more cell death when cells are co-treated with CQ but significantly reduced cell death when cells are co-treated with GSK, C3-I, or INO-1001 (INO) (Figure 6D), supporting that PERK, caspase-3, PARP-1 cleavage all contribute to cell death caused by Dox plus Crizo. This evidence concerns the gene EIF2AK3 and hepatocellular carcinoma.