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

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.

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