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Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 3, p e90062 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science, 2014.
-
Abstract
- 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.
- Subjects :
- Mouse
Colorectal cancer
Radiation Biophysics
Biophysics
lcsh:Medicine
Gastroenterology and Hepatology
Biochemistry
Rectal Cancer
Model Organisms
Western blot
Radioresistance
Molecular Cell Biology
Gastrointestinal Tumors
medicine
Akt Signaling Cascade
Gene silencing
Signaling in Cellular Processes
lcsh:Science
Protein kinase B
Biology
chemistry.chemical_classification
Reactive oxygen species
Multidisciplinary
medicine.diagnostic_test
Radiotherapy
lcsh:R
Cancers and Neoplasms
Antiapoptotic Signaling
Animal Models
medicine.disease
Molecular biology
Signaling Cascades
chemistry
Oncology
Apoptosis
Immunologic Techniques
Immunohistochemistry
Medicine
lcsh:Q
Clinical Immunology
Surgery
Radiology
Immunohistochemical Analysis
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c95cf31146b477004021dfa7bcab61d0