Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma

Despite multiple antitumor activities, interferon-alpha (IFN alpha) therapy alone is less effective in solid tumors. Autophagy has been reported to play a key role in tumor chemoresistance. Therefore, it is meaningful to explore whether autophagy can be activated by IFN alpha in head and neck squamous cell carcinoma (HNSCC) and serve as a potential target to improve efficacy of IFN alpha therapy. In this study, we report that IFN alpha not only exhibits anti proliferation activity and induces apoptosis, but also activates autophagy in HNSCC cells. Moreover, silencing autophagy-related protein 5 (ATG5) and signal transducer and activator of transcription 1 (STAT1) suppresses autophagy flux. Furthermore, IFN alpha and autophagy inhibitors (hydroxychloroquine and wortmannin) show clear synergistic effects on inhibiting growth and promoting apoptosis in HNSCC cells and xenograft models. Our findings indicate that IFN alpha-induced autophagy plays a cytoprotective role and blocking autophagy flux promotes IFN alpha-mediated apoptosis in HNSCC. These results suggest that the combination of IFN alpha and autophagy inhibitors represents a novel strategy for HNSCC treatment.