As the PI3K/Akt pathway regulates the expression of Nrf2, and as we previously found that FNDC5 affects the PI3K/Akt pathway, we evaluated the changes in the expression of PI3K, Akt, and Nrf2 in sorafenib-sensitive HCC, sorafenib-resistant, and FNDC5-knockdown resistant cell lines following treatment with the same concentration of sorafenib (Figure 4B). Here, FNDC5 is linked to hepatocellular carcinoma.