Erschienen in:
01.09.2014 | Original article
Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis
verfasst von:
Dr. rer. nat. Andrea Arenz, Ph.D., Frank Ziemann, Christina Mayer, Andrea Wittig, M.D., Kirstin Dreffke, Ph.D., Stefanie Preising, Steffen Wagner, Ph.D., Prof. Jens-Peter Klussmann, M.D., Prof. Rita Engenhart-Cabillic, M.D., Claus Wittekindt
Erschienen in:
Strahlentherapie und Onkologie
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Ausgabe 9/2014
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Abstract
Background and purpose
Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx.
Methods
Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated.
Results
HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22–0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45–0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs.
Conclusions
The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair.