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Inhibition of EGFR nuclear shuttling decreases irradiation resistance in HeLa cells
Affiliations- Central Laboratory of Weifang Hospital of Traditional Chinese Medicine, Weifang, Shangdong Province, China
open access
Abstract
Introduction. Cervical cancer is a leading cause of mortality in women worldwide. The resistance to irradiation at the advanced stage is the main reason for the poor prognosis and high mortality. This work aims to elucidate the molecular mechanism underlying the radio-resistance.
Material and methods. In this study, we determined the pEGFR-T654 and pDNA-PK-T2609 expression level changes in irradiated HeLa cells treated with T654 peptide, a nuclear localization signal (NLS) inhibitor, to inhibit EGFR nuclear transport. Cell viability, cell cycle and migratory capacity were analyzed. Xenograft animal model was used to evaluate the effect of EGFR nuclear transport inhibition on the tumor growth in vivo.
Results. The enhanced translocation of nuclear EGFR in the irradiated HeLa cells correlated with the increasing level of pEGFR-T654 and pDNA-PK-T2609. Inhibition of EGFR nuclear translocation by NLS peptide inhibitor attenuated DNA damage repair in the irradiated HeLa cells, decreased cell viability and promoted cell death through arrest at G0 phase. NLS peptide inhibitor impaired the migratory capacity of irradiated HeLa cells, and negatively affected tumorigenesis in xenograft mice.
Conclusions. This work puts forward a potential molecular mechanism of the irradiation resistance in cervical cancer cells, providing a promising direction towards an efficient therapy of cervical cancer.
Abstract
Introduction. Cervical cancer is a leading cause of mortality in women worldwide. The resistance to irradiation at the advanced stage is the main reason for the poor prognosis and high mortality. This work aims to elucidate the molecular mechanism underlying the radio-resistance.
Material and methods. In this study, we determined the pEGFR-T654 and pDNA-PK-T2609 expression level changes in irradiated HeLa cells treated with T654 peptide, a nuclear localization signal (NLS) inhibitor, to inhibit EGFR nuclear transport. Cell viability, cell cycle and migratory capacity were analyzed. Xenograft animal model was used to evaluate the effect of EGFR nuclear transport inhibition on the tumor growth in vivo.
Results. The enhanced translocation of nuclear EGFR in the irradiated HeLa cells correlated with the increasing level of pEGFR-T654 and pDNA-PK-T2609. Inhibition of EGFR nuclear translocation by NLS peptide inhibitor attenuated DNA damage repair in the irradiated HeLa cells, decreased cell viability and promoted cell death through arrest at G0 phase. NLS peptide inhibitor impaired the migratory capacity of irradiated HeLa cells, and negatively affected tumorigenesis in xenograft mice.
Conclusions. This work puts forward a potential molecular mechanism of the irradiation resistance in cervical cancer cells, providing a promising direction towards an efficient therapy of cervical cancer.
Keywords
EGFR; HeLa; nuclear translocation; pEGFR-T654; pDNA-PK-T2609; NLS peptide inhibitor; cell migration; xenograft
About this articleTitle
Inhibition of EGFR nuclear shuttling decreases irradiation resistance in HeLa cells
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Original paper
Pages
43-51
Published online
2017-05-18
Page views
1641
Article views/downloads
1604
DOI
Pubmed
Bibliographic record
Folia Histochem Cytobiol 2017;55(2):43-51.
Keywords
EGFR
HeLa
nuclear translocation
pEGFR-T654
pDNA-PK-T2609
NLS peptide inhibitor
cell migration
xenograft
Authors
Hong Wei
Zijie Zhu
Longtao Lu
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