DSF/Cu promotes cell death of hepatocellular carcinoma by inducing oxidative stress and downregulating PTEN/Akt signaling pathway
Objective To investigate the effect and underlying mechanism of disulfiram/copper(DSF/Cu)on the cell viability and proliferation of hepatocellular carcinoma(HCC).Methods HCC cell line HUH-7 was treated with different concentrations of DSF/Cu 0,0.25,0.50 and 1.00 μmol/L,and the cell viability was measured by CCK-8 method.The cell proliferation was observed by immunofluorescence.The contents of reactive oxygen species(ROS)and malondialdehyde(MDA)were determined by flow cytometry and colorimetry,respectively.The protein expressions ofγ-H2AX,PTEN,Akt and p-Akt were detected by Western blot.Then HCC cells were treated with the combination of DSF/Cu 0.50 μmol/L and GSH 1.0 mmol/L or MitoQ 1.0 μmol/L,and the cell viability,proliferation and content of ROS were observed.Results DSF/Cu could significantly inhibit the viability and proliferation of HUH-7 cells,increase the contents of ROS and MDA,upregulate the protein expressions of y-H2AX and PTEN,and downregulate the protein expression of p-Akt(P＜0.05).The content of ROS was decreased,and the cell viability and proliferation were increased after the treatment of antioxidant GSH or MitoQ(P＜0.05).Conclusion DSF/Cu can inhibit the viability and proliferation of HCC cells by promoting the oxidative stress response and downregulating the PTEN/Akt signaling pathway.
DisulfiramCopperHepatocellular carcinomaOxidative stressPhosphatase and tensin homolog deleted on chromosome 10Akt
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