Radio-sensitization of head and neck cancer cells by a combination of poly(I:C) and cisplatin through downregulation of survivin and c-IAP2

Cell Oncol (Dordr). 2019 Feb;42(1):29-40. doi: 10.1007/s13402-018-0403-7. Epub 2018 Sep 4.

Abstract

Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Concurrent radio-chemotherapy is the standard of care for advanced tumors. However, there is a need for more efficient regimens with less side effects resulting from high doses. Therefore, we set out to explore the therapeutic potential of ternary combinations by bringing together irradiation, cis-platinum and a TLR3 agonist, poly(I:C), with the aim to reduce the dosage of each treatment. This approach is based on our previous work, which revealed a selective cytotoxic effect of TLR3 agonists against malignant cells when combined with other anti-neoplastic agents.

Methods: We explored the survival of HNSCC-derived cells (Detroit 562, FaDu, SQ20B and Cal27) using MTT and caspase 3/7 activation assays. The radio-sensitization effects of poly(I:C) and cisplatin were assessed using Western blotting, cell cycle progression, ROS formation and qRT-PCR assays.

Results: We found that the combination of poly(I:C) and cisplatin downregulated c-IAP2 and survivin expression, reduced cell survival, induced anti-apoptotic gene expression and apoptosis, increased ROS formation and induced G2/M cell cycle arrest in the HNSCC-derived cells tested.

Conclusions: Our results indicate that a combined poly(I:C) and cisplatin treatment reduces the survival and induces the radio-sensitivity of HNSCC-derived cells, thus providing a rationale for the development of novel strategies for the treatment of head and neck cancer.

Keywords: Cisplatin; Head and neck cancer; Poly(I:C); Radio-sensitization; TLR3; Therapy.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cisplatin / pharmacology*
  • Down-Regulation / drug effects*
  • Down-Regulation / radiation effects
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Poly I-C / pharmacology*
  • Radiation Tolerance / drug effects*
  • Radiation Tolerance / radiation effects
  • Reactive Oxygen Species / metabolism
  • Survivin / genetics*
  • Survivin / metabolism

Substances

  • Inhibitor of Apoptosis Proteins
  • Reactive Oxygen Species
  • Survivin
  • Poly I-C
  • Cisplatin