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Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way
Human phosphatidylethanolamine-binding protein 4(hPEBP4) is a novel anti-apoptosis molecule associated with the resistance of tumors to apoptotic agents. Here we sought to investigate the role of hPEBP4 in the radioresistance of rectal cancer. Immunohistochemistry analysis showed hPEBP4 was expresse...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940727/ https://www.ncbi.nlm.nih.gov/pubmed/24594691 http://dx.doi.org/10.1371/journal.pone.0090062 |
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author | Qiu, Jianming Yang, Guangen Lin, Ali Shen, Zhong Wang, Dong Ding, Lei |
author_facet | Qiu, Jianming Yang, Guangen Lin, Ali Shen, Zhong Wang, Dong Ding, Lei |
author_sort | Qiu, Jianming |
collection | PubMed |
description | Human phosphatidylethanolamine-binding protein 4(hPEBP4) is a novel anti-apoptosis molecule associated with the resistance of tumors to apoptotic agents. Here we sought to investigate the role of hPEBP4 in the radioresistance of rectal cancer. Immunohistochemistry analysis showed hPEBP4 was expressed in 27/33 of rectal cancer specimens, but only in 2/33 of neighboring normal mucosa. Silencing the expression of hPEBP4 with siRNA significantly reduced the clonogenic survival and enhanced the apoptosis of rectal cancer cells on irradiation. Instead, forced overexpression of hPEBP4 promoted its survival and decreased the apoptosis. Western blot showed hPEBP4 could increase the radiation-induced Akt activation, for which reactive oxygen specimen(ROS) was required. The radioresistance effect of hPEBP4 was reversed after given LY-294002 to inhibit Akt activation or antioxidant to abolish the ROS production. We also confirmed that effect of hPEBP4 in vivo with nude mice. Thus we concluded that hPEBP4, specifically expressed in rectal cancer cells, is associated with radioresistance of rectal cancer, implying that modulation of hPEBP4 may have important therapeutic implications in radiotherapy of rectal cancer. |
format | Online Article Text |
id | pubmed-3940727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39407272014-03-06 Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way Qiu, Jianming Yang, Guangen Lin, Ali Shen, Zhong Wang, Dong Ding, Lei PLoS One Research Article Human phosphatidylethanolamine-binding protein 4(hPEBP4) is a novel anti-apoptosis molecule associated with the resistance of tumors to apoptotic agents. Here we sought to investigate the role of hPEBP4 in the radioresistance of rectal cancer. Immunohistochemistry analysis showed hPEBP4 was expressed in 27/33 of rectal cancer specimens, but only in 2/33 of neighboring normal mucosa. Silencing the expression of hPEBP4 with siRNA significantly reduced the clonogenic survival and enhanced the apoptosis of rectal cancer cells on irradiation. Instead, forced overexpression of hPEBP4 promoted its survival and decreased the apoptosis. Western blot showed hPEBP4 could increase the radiation-induced Akt activation, for which reactive oxygen specimen(ROS) was required. The radioresistance effect of hPEBP4 was reversed after given LY-294002 to inhibit Akt activation or antioxidant to abolish the ROS production. We also confirmed that effect of hPEBP4 in vivo with nude mice. Thus we concluded that hPEBP4, specifically expressed in rectal cancer cells, is associated with radioresistance of rectal cancer, implying that modulation of hPEBP4 may have important therapeutic implications in radiotherapy of rectal cancer. Public Library of Science 2014-03-03 /pmc/articles/PMC3940727/ /pubmed/24594691 http://dx.doi.org/10.1371/journal.pone.0090062 Text en © 2014 Qiu 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 Qiu, Jianming Yang, Guangen Lin, Ali Shen, Zhong Wang, Dong Ding, Lei Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way |
title | Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way |
title_full | Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way |
title_fullStr | Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way |
title_full_unstemmed | Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way |
title_short | Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way |
title_sort | human phosphatidylethanolamine-binding protein 4 promoted the radioresistance of human rectal cancer by activating akt in an ros-dependent way |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940727/ https://www.ncbi.nlm.nih.gov/pubmed/24594691 http://dx.doi.org/10.1371/journal.pone.0090062 |
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