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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma

Published on: January 5, 2017

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

Wenyi Yang1, Chunlan Jiang2, Weiya Xia3

  • 1Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai, 200011, China.

Cancer Letters
|March 14, 2019
PubMed

Insights

Interferon-alpha (IFNα) activates protective autophagy in head and neck cancer. Combining IFNα with autophagy inhibitors enhances anti-cancer effects, offering a new treatment strategy for HNSCC.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Interferon-alpha (IFNα) shows antitumor activity but limited efficacy in solid tumors.
  • Autophagy is implicated in tumor chemoresistance.
  • Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy.

Purpose of the Study:

  • To investigate IFNα-induced autophagy in HNSCC.
  • To determine if autophagy is a targetable mechanism to enhance IFNα therapy for HNSCC.

Main Methods:

  • IFNα treatment on HNSCC cell lines.
  • Assessment of proliferation, apoptosis, and autophagy.
  • Silencing of autophagy-related protein 5 (ATG5) and signal transducer and activator of transcription 1 (STAT1).
  • Combination therapy with IFNα and autophagy inhibitors (hydroxychloroquine, wortmannin) in vitro and in vivo.

Main Results:

  • IFNα demonstrated anti-proliferative and pro-apoptotic effects in HNSCC cells.
  • IFNα treatment activated autophagy in HNSCC.
  • Silencing ATG5 and STAT1 inhibited autophagy flux.
  • Combination therapy synergistically inhibited HNSCC growth and promoted apoptosis.

Conclusions:

  • IFNα-induced autophagy plays a cytoprotective role in HNSCC.
  • Blocking autophagy flux potentiates IFNα-mediated apoptosis.
  • Combination of IFNα and autophagy inhibitors is a promising therapeutic strategy for HNSCC.
Keywords:
AutophagyHead and neck squamous cell carcinomaHydroxychloroquineInterferon-alphaWortmannin

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