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Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair
BACKGROUND: Nimotuzumab is a humanized IgG1 monoclonal antibody specifically targeting EGFR. In this study, we aimed to investigate the molecular mechanisms of nimotuzumab in its effects of enhancing cancer cell radiosensitivity. PRINCIPAL FINDING: Lung cancer A549 cells and breast cancer MCF-7 cell...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745376/ https://www.ncbi.nlm.nih.gov/pubmed/23976954 http://dx.doi.org/10.1371/journal.pone.0070727 |
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author | Qu, Yuan-yuan Hu, Song-liu Xu, Xiang-ying Wang, Rui-zhi Yu, Hong-yang Xu, Jian-yu Chen, Lin Dong, Guang-lu |
author_facet | Qu, Yuan-yuan Hu, Song-liu Xu, Xiang-ying Wang, Rui-zhi Yu, Hong-yang Xu, Jian-yu Chen, Lin Dong, Guang-lu |
author_sort | Qu, Yuan-yuan |
collection | PubMed |
description | BACKGROUND: Nimotuzumab is a humanized IgG1 monoclonal antibody specifically targeting EGFR. In this study, we aimed to investigate the molecular mechanisms of nimotuzumab in its effects of enhancing cancer cell radiosensitivity. PRINCIPAL FINDING: Lung cancer A549 cells and breast cancer MCF-7 cells were pretreated with or without nimotuzumab for 24 h before radiation to perform the clonogenic survival assay and to analyze the cell apoptosis by flow ctyometry. γ-H2AX foci were detected by confocal microscopy to assess the effect of nimotuzumab on radiation induced DNA repair. EGFR activation was examined and the levels of DNA damage repair related proteins in A549 cells at different time point and at varying doses exposure after nimotuzumab and radiation treatment were examined by Western blot. Pretreatment with nimotuzumab reduced clonogenic survival after radiation, inhibited radiation-induced EGFR activation and increased the radiation-induced apoptosis in both A549 cells and MCF-7 cells. The foci of γ-H2AX 24 h after radiation significantly increased in nimotuzumab pretreated cells with different doses. The phosphorylation of AKT and DNA-PKcs were remarkably inhibited in the combination group at each dose point as well as time point. CONCLUSIONS: Our results revealed that the possible mechanism of nimotuzumab enhancing the cancer radiosensitivity is that nimotuzumab inhibited the radiation-induced activation of DNA-PKcs through blocking the PI3K/AKT pathway, which ultimately affected the DNA DSBs repair. |
format | Online Article Text |
id | pubmed-3745376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37453762013-08-23 Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair Qu, Yuan-yuan Hu, Song-liu Xu, Xiang-ying Wang, Rui-zhi Yu, Hong-yang Xu, Jian-yu Chen, Lin Dong, Guang-lu PLoS One Research Article BACKGROUND: Nimotuzumab is a humanized IgG1 monoclonal antibody specifically targeting EGFR. In this study, we aimed to investigate the molecular mechanisms of nimotuzumab in its effects of enhancing cancer cell radiosensitivity. PRINCIPAL FINDING: Lung cancer A549 cells and breast cancer MCF-7 cells were pretreated with or without nimotuzumab for 24 h before radiation to perform the clonogenic survival assay and to analyze the cell apoptosis by flow ctyometry. γ-H2AX foci were detected by confocal microscopy to assess the effect of nimotuzumab on radiation induced DNA repair. EGFR activation was examined and the levels of DNA damage repair related proteins in A549 cells at different time point and at varying doses exposure after nimotuzumab and radiation treatment were examined by Western blot. Pretreatment with nimotuzumab reduced clonogenic survival after radiation, inhibited radiation-induced EGFR activation and increased the radiation-induced apoptosis in both A549 cells and MCF-7 cells. The foci of γ-H2AX 24 h after radiation significantly increased in nimotuzumab pretreated cells with different doses. The phosphorylation of AKT and DNA-PKcs were remarkably inhibited in the combination group at each dose point as well as time point. CONCLUSIONS: Our results revealed that the possible mechanism of nimotuzumab enhancing the cancer radiosensitivity is that nimotuzumab inhibited the radiation-induced activation of DNA-PKcs through blocking the PI3K/AKT pathway, which ultimately affected the DNA DSBs repair. Public Library of Science 2013-08-16 /pmc/articles/PMC3745376/ /pubmed/23976954 http://dx.doi.org/10.1371/journal.pone.0070727 Text en © 2013 Qu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Qu, Yuan-yuan Hu, Song-liu Xu, Xiang-ying Wang, Rui-zhi Yu, Hong-yang Xu, Jian-yu Chen, Lin Dong, Guang-lu Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair |
title | Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair |
title_full | Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair |
title_fullStr | Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair |
title_full_unstemmed | Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair |
title_short | Nimotuzumab Enhances the Radiosensitivity of Cancer Cells In Vitro by Inhibiting Radiation-Induced DNA Damage Repair |
title_sort | nimotuzumab enhances the radiosensitivity of cancer cells in vitro by inhibiting radiation-induced dna damage repair |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745376/ https://www.ncbi.nlm.nih.gov/pubmed/23976954 http://dx.doi.org/10.1371/journal.pone.0070727 |
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