Abstract

Purpose:To test the anti-tumor efficacy of doxorubicin (Dox) in combination with IFN-γ on Hepatocarcinoma 22 (H22) cells in vitro and in vivo. Methods: 50% inhibition concentration (IC₅₀) of Dox with or without IFN-γ pretreatment was firstly determined in vitro. The in vivo therapeutic efficacy of various administration regimes of IFN-γ and pegylated liposomal Dox (PLD) was investigated in H22 tumor bearing mice model. Results: IC₅₀ of Dox was significantly reduced with IFN-γ pretreatment (5-fold reduction), which indicated a potentiated cytotoxicity of Dox with a synergistic manner in H22 cells. The free or liposomal IFN-γ pretreatment followed by PLD administration almost completely inhibited the tumor growth in vivo with tumor inhibition rates more than 90%, significantly higher than that of the mono-therapy with PLD (76.25%). Conclusion: The pretreatment with IFN-γ as chemosensitizer before the administration of PLD may be a promising approach to HCC therapy with direct and immediate clinical benefits.


Keywords:  Interferon-γ   Doxorubicin   Pegylated liposomal Dox   Hepatocellular carcinoma   Antiproliferative activity