Effect of sinomenine combined with sorafenib on the proliferation,migration and apoptosis of hepatocellular carcinoma HepG2 cells
Objective To investigate the synergistic inhibitory effect and potential mechanism of sinomenine and sorafenib on the biological function of HepG2 cells in hepatocellular carcinoma.Methods The effects of two drugs alone and in combination on the proliferation,migration,and apoptosis of HepG2 cells were evaluated by MTT,plate cloning,cell scratch,Transwell and Hoechst 33342/PI double staining experiments.The changes of ROS expression in HepG2 cells after treatment with the various groups of drugs were detected by the ROS kit.Molecular docking technique was used to predict the potential binding of sinomenine and sorafenib as the main targets of anti-liver cancer.Western blot was used to detect the expression of VEGFR2,STAT3,and p-STAT3 proteins in the combination therapy group,as well as the downstream protein expression of MMP2,MMP9,BCL-2,BAX,and cleared Caspase3.Results Both sinomenine and sorafenib significantly inhibited the survival of HepG2 cells in a time-and dose-dependent manner(P<0.05).The results of MTT,plate cloning,cell scratch,Transwell and Hoechst 33342/PI double staining experiments showed that the combination of the two drugs can synergistically inhibit cell proliferation and migration,and promote cell apoptosis in HepG2 cells.The combination therapy group significantly enhanced the expression of ROS compared to the monotherapy group.The molecular docking and western blot results showed that the combination therapy group inhibited the expression of VEGFR2 and p-STAT3,and reduced the expression of migration key proteins MMP2 and MMP9,upregulated the BAX/BCL-2 ratio,and the expression of cleared Caspase3(P<0.05).Conclusion The combination of sinomenine and sorafenib can synergistically inhibit the proliferation and migration of HepG2 cells and induce cell apoptosis in vitro,which may be related to the downregulation of the VEGFR2/STAT3 pathway and downstream related molecules.
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