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Cellular Oncology

, Volume 42, Issue 1, pp 29–40 | Cite as

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

  • Martina Mikulandra
  • Antonio Kobescak
  • Benjamin Verillaud
  • Pierre Busson
  • Tanja Matijevic GlavanEmail author
Original Paper
  • 86 Downloads

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

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

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13402_2018_403_MOESM1_ESM.docx (25 kb)
ESM 1 (DOCX 25 kb)

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Copyright information

© International Society for Cellular Oncology 2018

Authors and Affiliations

  1. 1.Laboratory for Personalized Medicine, Division of Molecular MedicineRudjer Boskovic InstituteZagrebCroatia
  2. 2.Department of Radiotherapy and Medical OncologyUniversity Hospital for Tumors, University Hospital Centre Sisters of MercyZagrebCroatia
  3. 3.University Paris-Sud 11, CNRS-UMR 8126, Institut Gustave RoussyVillejuif cedexFrance
  4. 4.Department of Head and Neck surgery, Lariboisière Hospital, AP-HPUniversity Paris-Diderot Paris 7ParisFrance

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