Combination of interferon-gamma and autophagy inhibitor as a therapeutic approach in oral squamous cell carcinoma

Abstract Background: Former clinical trials and experimental research have indicated that interferon-gamma (IFNγ) therapy does not achieve an ideal effect in solid tumors. Autophagy has been associated with tumor chemoresistance. The aim of this study was to explore the efficacy of IFNγ and autophagy inhibitor in the combination treatment of oral squamous cell carcinoma (OSCC). Method: IFNγ-induced apoptosis was evaluated by the expression of relative proteins (cleaved-PARP and caspase-3) and flow cytometry. IFNγ-induced autophagy was assessed by the expression of Beclin1, LC3B, and P62. The synergistic effect of IFNγ and autophagy inhibitor (chloroquine) was evaluated in vitro and in vivo . Findings: IFNγ induced anti-proliferation, apoptosis, and autophagy in OSCC cells. Autophagy-related protein 5 (ATG5) was a key feature in IFNγ-induced autophagy flux. IFNγ and chloroquine had obvious synergistic effects on cellular growth inhibition and apoptosis promotion in OSCC cells and xenograft models. Interpretation: Our findings suggest that IFNγ-induced autophagy plays a cellular protective role, and blocking autophagy flux can promote IFNγ-mediated OSCC cell apoptosis. The combination of IFNγ and autophagy inhibitors represents a novel strategy for OSCC therapy.