Objective      To investigate the synergistic effect of dichloroacetate (DCA) and pirarubicin (THP) in hepatocellular carcinoma (HCC) cells and the possible mechanism.       Methods      HepG2 cells were treated with DCA (40 μmol/L) combined with THP with different concentrations (0

200

400

600

and 800 μmol/L) for 24 h

and then CCK-8 assay was used to detect the cell viability. Moreover

the cells were treated with or without 600 μmol/L of THP in the presence or absence of 40 μmol/L of DCA. Then Western blotting was utilized to measure the expression of cellular molecules

and DCFH-DA fluorescent probes were used to estimate the level of reactive oxygen species (ROS).       Results      Compared with PBS

DCA significantly enhanced the cytotoxicity of THP in HepG2 cells (P0.05). The combination of DCA and THP induced an obvious increase of ROS compared with the combination of PBS and THP (P0.05). Moreover

the combination of DCA and THP obviously increased the cleavage of PARP and the phosphorylation of JNK. Antioxidant NAC could significantly inhibit JNK phosphorylation in HepG2 cells treated with DCA and THP.       Conclusion      DCA significantly enhances the cytotoxicity of THP in HCC cells

which may be dependent on the activation of ROS/JNK signaling pathway.