OBJECTIVETo investigate the inhibitory effect of sorafenib in combination with arsenic trioxide (As2O3) on hepatocellular carcinoma cells and explore the mechanisms of the synergetic antitumor effects of the two agents.

METHODSHepG2 cells were treated with sorafenibor, As2O3 alone or their combination, with the untreated cells used as the control. The inhibitory effect of the treatment was analyzed by MTT assay, and the cell apoptosis and mitochondrial transmembrane potential (delta phi m) were detected by flow cytometry. Western blotting was performed to examine the expressions of ERK and pERK in the cells.

RESULTSSorafenib and As2O3 used alone or in combination both inhibited the proliferation of HepG2 cells, and a synergistic effect of the two agents was noted in their combined action (P<0.05). Combined treatment of the cells resulted in significantly higher apoptsis rate than that in the other groups (P<0.05), and was associated with a more obvious decrease in delta phi m. The expression of ERK was not affected by the two agents used either alone or in combination, but pERK expression was significantly lowered in the cells after combined treatment for 24 h.

CONCLUSIONA synergistic effect is observed between the sorafenib and As2O3 in their inhibition of HepG2 cell proliferation, the mechanisms of which may involve reduction of mitochondrial transmembrane potential and Raf/MEK/ERK pathway inhibition.