Hypoxia induces radioresistance, epithelial‑mesenchymal transition, cancer stem cell‑like phenotype and changes in genes possessing multiple biological functions in head and neck squamous cell carcinoma.

Content Provider	Europe PMC
Author	Wiechec, Emilia Matic, Natasa Ali, Ashfaq Roberg, Karin
Copyright Year	2022
Abstract	Hypoxia has been linked with increased resistance to treatment in various solid tumors, including head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to identify genes involved in hypoxia-mediated responses to radiotherapy in HNSCC. A total of three HNSCC cell lines with an epithelial phenotype were selected for this study and cultured under normoxic (21% O2) or hypoxic (1% O2) conditions. The sensitivity of the HNSCC cells to radiotherapy was assessed by a crystal violet assay. Western blotting (for protein expression), cDNA microarrays and reverse transcription-quantitative PCR (for gene expression) were also applied. Small interfering RNA silencing was used to knock down target genes. The results revealed that hypoxia negatively affected the response of HNSCC cells to radiotherapy. Of note, increased levels of N-cadherin, vimentin and fibronectin, as well as stem cell-associated transcription factors, were observed under hypoxia. The microarray analysis revealed a number of hypoxia-regulated genes that were involved in multiple biological functions. However, downregulation of hypoxia-regulated genes did not affect sensitivity to radiotherapy of the investigated cell lines. Taken together, the present findings indicated several important pathways and genes that were involved in hypoxia and radiotherapy resistance. It is hypothesized that panels of reported hypoxia-regulated genes may be useful for the prediction of radiotherapy responses in patients with HNSCC.
ISSN	1021335X
Journal	Oncology Reports
Volume Number	47
PubMed Central reference number	PMC8808704
Issue Number	3
PubMed reference number	35059742
e-ISSN	17912431
DOI	10.3892/or.2022.8269
Language	English
Publisher	D.A. Spandidos
Publisher Date	2022-01-21
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Wiechec et al.
Subject Keyword	hypoxia epithelial-mesenchymal transition head and neck cancer radiotherapy microarray
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology