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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

Wiechec, Emilia ; Matic, Natasa ; Ali, Ashfaq LU orcid and Roberg, Karin (2022) In Oncology Reports 47(3).
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... (More)

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.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epithelial?mesenchymal transition, Head and neck cancer, hypoxia, Microarray, Radiotherapy
in
Oncology Reports
volume
47
issue
3
article number
8269
publisher
Spandidos Publications
external identifiers
  • scopus:85123314051
  • pmid:35059742
ISSN
1021-335X
DOI
10.3892/or.2022.8269
language
English
LU publication?
yes
id
c299d71e-1dbc-4d8a-bdc9-3c4e51bc504b
date added to LUP
2022-03-17 12:53:59
date last changed
2024-04-04 04:15:14
@article{c299d71e-1dbc-4d8a-bdc9-3c4e51bc504b,
  abstract     = {{<p>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.</p>}},
  author       = {{Wiechec, Emilia and Matic, Natasa and Ali, Ashfaq and Roberg, Karin}},
  issn         = {{1021-335X}},
  keywords     = {{Epithelial?mesenchymal transition; Head and neck cancer; hypoxia; Microarray; Radiotherapy}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{Spandidos Publications}},
  series       = {{Oncology Reports}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.3892/or.2022.8269}},
  doi          = {{10.3892/or.2022.8269}},
  volume       = {{47}},
  year         = {{2022}},
}