The inhibitory effect of sorafenib together with oxaliplatin on the growth of human hepatic carcinoma cell line HepG2 in vitro

Objective To investigate the inhibitory effect of sorafenib in combination use with oxaliplatin(L-OHP) on the proliferation of hepatocellular carcinoma cells and to explore the possible molecular mechanism.Methods The inhibitory effect of sorafenib together with L-OHP on the growth of human hepatic carcinoma cell line HepG2 in vitro was evaluated by CCK8 assay.The cell cycle changes and the apoptotic rate of the treated cells were determined by flow cytometry,and the expressions of ERK and pERK were observed by using Western blott.Results Both sorafenib and L-OHP when used alone could significantly inhibit the proliferation of HepG2 cells,and a synergistic or adding effect could be achieved when both sorafenib and L-OHP were used together(P 0.05).Sorafenib and L-OHP could cause cell cycle to stagnate at G1 phase and S phase,respectively.Combined use of the two drugs resulted in cell cycle arresting at G1 phase and S phase.The combination use of the drugs significantly increased the apoptosis rate of the cells as compared with that when only sorafenib or L-OHP was used(P 0.05).Sorafenib and L-OHP,whether used alone or in combination,did not produce obvious effect on ERK expression.However,pERK expression in the HepG2 cells was significantly lowered after the treatment with sorafenib alone or in combination with L-OHP,especially in the combination use group.Conclusion The combination use of sorafenib and L-OHP shows a synergistic or adding effect in inhibiting the proliferation and inducing apoptosis of HepG2 cells.The mechanism of this synergistic effect may be closely related to the double blockage of the cell cycle as well as to the inhibition of Raf/MEK/ERK pathway.