Chronic oxidative stress adaptation in head and neck cancer cells generates slow-cyclers with decreased tumour growth in vivo.

Autor: Berner J; Department of Oral, Maxillofacial, and Plastic Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str, 17475, Greifswald, Germany.; ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany., Miebach L; ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany.; Department of General, Visceral, Thoracic, and Vascular Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str, 17475, Greifswald, Germany., Kordt M; Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany., Seebauer C; Department of Oral, Maxillofacial, and Plastic Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str, 17475, Greifswald, Germany., Schmidt A; ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany., Lalk M; Institute for Biochemistry, University of Greifswald, Felix-Hausdorff-Str. 4, 17489, Greifswald, Germany., Vollmar B; Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany., Metelmann HR; Department of Oral, Maxillofacial, and Plastic Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str, 17475, Greifswald, Germany., Bekeschus S; ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany. sander.bekeschus@inp-greifswald.de.; Clinic and Policlinic for Dermatology and Venerology, Rostock University Medical Center, Strempelstr. 13, 18057, Rostock, Germany. sander.bekeschus@inp-greifswald.de.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2023 Sep; Vol. 129 (5), pp. 869-883. Date of Electronic Publication: 2023 Jul 17.
DOI: 10.1038/s41416-023-02343-6
Abstrakt: Background: Reactive oxygen species (ROS) are implicated in cancer therapy and as drivers of microenvironmental tumour cell adaptations. Medical gas plasma is a multi-ROS generating technology that has been shown effective for palliative tumour control in head and neck cancer (HNC) patients before tumour cells adapted to the oxidative stress and growth regressed fatally.
Methods: In a bedside-to-bench approach, we sought to explore the oxidative stress adaptation in two human squamous cell carcinoma cell lines. Gas plasma was utilised as a putative therapeutic agent and chronic oxidative stress inducer.
Results: Cellular responses of single and multiple treated cells were compared regarding sensitivity, cellular senescence, redox state and cytokine release. Whole transcriptome analysis revealed a strong correlation of cancer cell adaption with increased interleukin 1 receptor type 2 (IL1R2) expression. Using magnetic resonance imaging, tumour growth and gas plasma treatment responses of wild-type (WT) and repeatedly exposed (RE) A431 cells were further investigated in a xenograft model in vivo. RE cells generated significantly smaller tumours with suppressed inflammatory secretion profiles and increased epidermal growth factor receptor (EGFR) activity showing significantly lower gas plasma sensitivity until day 8.
Conclusions: Clinically, combination treatments together with cetuximab, an EGFR inhibitor, may overcome acquired oxidative stress resistance in HNC.
(© 2023. The Author(s).)
Databáze: MEDLINE
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