Synergistic activity of magnolin combined with B-RAF inhibitor SB590885 in hepatocellular carcinoma cells via targeting PI3K-AKT/mTOR and ERK MAPK pathway.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains obscure. From a clinical point of view, the ERK MAPK pathway and the PI3K/AKT pathway are activated in the majority of liver cancer. In addition, long term used to single agent treatment of HCC, frequently results in reverse activation of the ERK MAPK pathway or the PI3K/AKT pathway, leading to drug resistance. Thus, it is important to research the mechanism of combination agents that could suppress different pathways to treat HCC. Here, we found that combination natural product magnolin with BRAF inhibitor SB590885 synergistically suppressed the proliferation, promoted cell cycle arrest and apoptosis in hepatocellular carcinoma cells Bel-7402 and SK-Hep1. Furthermore, we demonstrated that the magnolin and the SB590885 combination led to increased impaired proliferation via inhibition of the ERK MAPK pathway and the PI3K/AKT pathway. These findings highlight the important role of agent combination and provided the approaches of therapeutic improvement for patients with advanced HCC.