AIM: To investigate the role of sorafenib (SFN) in autophagy of hepatocellular 
carcinoma (HCC). We evaluated how SFN affects autophagy signaling pathway in 
human HCC cell lines.
METHODS: Two different human HCC cell lines, Hep3B and Huh7, were subjected to 
different concentrations of SFN. Cell viability and onset of apoptosis were 
determined with colorimetric assay and immunoblotting analysis, respectively. 
The changes in autophagy-related proteins, including LC3, ULK1, AMPK, and LKB, 
were determined with immunoblotting analysis in the presence or absence of SFN. 
To assess autophagic dynamics, autophagic flux was measured with chloroquine, a 
lysosomal inhibitor. The autophagic responsiveness between different HCC cell 
lines was compared under the autophagy enhancing conditions.
RESULTS: Hep3B cells were significantly more resistant to SFN than Huh7 cells. 
Immunoblotting analysis revealed a marked increase in SFN-mediated autophagy 
flux in Huh7 cells, which was, however, absent in Hep3B cells. While both 
starvation and rapamycin enhanced autophagy in Huh7 cells, only rapamycin 
increased autophagy in Hep3B cells. Immunoblotting analysis of autophagy 
initiation proteins showed that SFN substantially increased phosphorylation of 
AMPK and consequently autophagy in Huh7, but not in Hep3B cells.
CONCLUSION: The autophagic responsiveness to SFN is distinct between Hep3B and 
Huh7 cells. Resistance of Hep3B cells to SFN may be associated with altered 
autophagy signaling pathways.