Moreover, SESN2 is found capable of inducing resistance to chemotherapeutic drugs through activating AKT signaling via the regulation of PTEN in human squamous cell carcinoma and melanoma cells.13 Identical to what previously studied, our study demonstrated that SESN2 was able to induce primary resistance to the targeted agent, sorafenib, in HCC cells via activating both AKT and AMPK, suggesting that SESN2 could be a novel target to limit HCC growth and to increase therapeutic sensitivity toward sorafenib. This evidence concerns the gene AKT1 and squamous cell carcinoma.