Abstract:

Objective To investigate the anti-proliferative effects of combining Sorafenib and sodium cantharidinate on HepG2 liver cancer cells. Methods HepG2 cells were treated with sorafenib alone， sodium cantharidinate alone or both together；control cells were left untreated. The CCK-8 assay was used to measure antiproliferative effects of different drug concentrations；flow cytometry，to measure cell cycle distribution； and Western blotting，to measure expression of ERK and pERK. Results Both sorafenib and sodium cantharidinate on their own or together inhibited HepG2 proliferation in a dose-dependent way，with the combination proving significantly more potent than either drug on its own （P＜0.05）. Combining the two drugs led to an additive antiproliferative effect，except at a concentration of 4 μmol/L of sorafenib and 3.88 μmol/L of sodium cantharidinate at 48 h，when a synergistic effect was observed. The proportion of cells arrested in G1 phase was significantly greater with either drug alone or both together than in the absence of drug（P<0.001），and it was significantly higher for the two drugs together than for either drug alone（P<0.05）. ERK was not significantly affected by either drug on its own or by the combination （P=0.1）， while pERK levels were significantly lower with sorafenib alone or both drugs together than in the absence of drug（P<0.05）. Conversely，the pERK level was significantly higher with sodium cantharidinate alone than in the absence of drug（P=0.023）. Conclusion The combination of sorafenib and sodium cantharidinate can exert a synergistic antiproliferative effect on HepG2 cells，and this effect may be due to cell cycle arrest and inhibition of the RAF/MEK/ERK signaling pathway.

Key words: Liver neoplasm, Sorafenib, Sodium cantharidinate, Anti-proliferative effects, Signaling pathway