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...

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Main Authors: Jianming Qiu, Guangen Yang, Ali Lin, Zhong Shen, Dong Wang, Lei Ding
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090062&type=printable
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author Jianming Qiu
Guangen Yang
Ali Lin
Zhong Shen
Dong Wang
Lei Ding
author_facet Jianming Qiu
Guangen Yang
Ali Lin
Zhong Shen
Dong Wang
Lei Ding
author_sort Jianming Qiu
collection DOAJ
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.
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spelling doaj.art-94a16aad0afb4d9680c84bf7cfe41c912025-02-21T05:36:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9006210.1371/journal.pone.0090062Human phosphatidylethanolamine-binding protein 4 promoted the radioresistance of human rectal cancer by activating Akt in an ROS-dependent way.Jianming QiuGuangen YangAli LinZhong ShenDong WangLei DingHuman 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090062&type=printable
spellingShingle Jianming Qiu
Guangen Yang
Ali Lin
Zhong Shen
Dong Wang
Lei Ding
Human phosphatidylethanolamine-binding protein 4 promoted the radioresistance of human rectal cancer by activating Akt in an ROS-dependent way.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090062&type=printable
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