Oncotarget

Research Papers:

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

Chia-Jung Busch, Benjamin Becker, Malte Kriegs, Fruzsina Gatzemeier, Katharina Krüger, Nikolaus Möckelmann, Gerhard Fritz, Cordula Petersen, Rainald Knecht, Kai Rothkamm and Thorsten Rieckmann _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:35832-35842. https://doi.org/10.18632/oncotarget.9028

Metrics: PDF 1667 views  |   HTML 4124 views  |   ?  


Abstract

Chia-Jung Busch1,*, Benjamin Becker1,2,*, Malte Kriegs2, Fruzsina Gatzemeier2, Katharina Krüger3, Nikolaus Möckelmann1, Gerhard Fritz3, Cordula Petersen4 and Rainald Knecht1, Kai Rothkamm2, Thorsten Rieckmann1,2

1 Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany

2 Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany

3 Institute of Toxicology, University Medical Center Düsseldorf, Düsseldorf, Germany

4 Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany

* These authors have contributed equally to this work

Correspondence to:

Thorsten Rieckmann, email:

Keywords: HPV, HNSCC, cisplatin

Received: December 09, 2015 Accepted: April 16, 2016 Published: April 26, 2016

Abstract

Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation.

While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 9028