Consistent with the in vitro results, we found that combined treatment with amiloride attenuated sorafenib-induced dextran uptake and staining of phosphorylated AKT and PAK1 in HCC tissues from SK-Hep1 or Huh7 xenograft tumors (Fig. 5E and Fig. S5G), which highlights the important role of inhibiting macropinocytosis in increasing the susceptibility of HCC to sorafenib. This evidence concerns the gene PAK1 and hepatocellular carcinoma.