Objective      To investigate the mechanism and significance of sorafenib-induced autophagy in HepG2 cell line.       Methods      HepG2 cells were transfected with GFP-LC3 plasmid to observe the effect of sorafenib on autophagosome formation. The interaction of Mcl-1 and Beclin1 was tested by co-immunoprecipitation (Co-IP). The anti-tumor effect of sorafenib was detected after autophagy inhibition with chloroquine(CQ) or knock down of autophagy-related gene Atg5 by siRNA. Changes of autophagic and apoptotic proteins Atg5

Beclin1

LC3

Mcl-1 and PARP were detected by Western blotting.       Results      In HepG2 cells

sorafenib upregulated LC3-Ⅱ protein expression in a dose-dependent manner. HepG2 cells transfected with GFP-LC3 plasmid showed autophogosome-like dot fluorescence when treated with sorafenib. Mcl-1 protein level was downregulated while Beclin1 remained unchanged when treated with sorafenib

as shown by Western blotting. The interaction between MCL-1 and Beclin1 were observed and could be reduced by sorafenib treatment

as shown by Co-IP. The anti-tumor effect of sorafenib was enhanced when autophagy was inhibited.       Conclusion      Sorafenib may induce autophagy by down-regulating Mcl-1 expression. The anti-tumor effect of sorafenib is enhanced when autophagy is inhibited.