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Heat Shock Protein 27-Targeted Heptapeptide of the PKCΔ Catalytic V5 Region Sensitizes Tumors with Radio- and Chemoresistance.
MedLine Citation:
PMID:  21300481     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Previous data suggest that the PKCδ catalytic V5 (PKCδ-V5) heptapeptide (HEPT) (FEQFLDI) binds HSP27 and blocks HSP27-mediated radio- or chemoresistance. Here we investigated further the in vivo function of the PKCδ-V5 HEPT. METHODS AND MATERIALS: Labeling of HEPT with Cy5.5 or fluorescein isothiocyanate was performed to evaluate in vitro or in vivo distribution of HEPT. A clonogenic survival assay, flow cytometry, and Western blotting of cleaved caspase-3 were performed to determine in vitro sensitization effects of HEPT plus ionizing radiation (IR) versus IR alone or those of HEPT plus cisplatin(Cis) versus Cis alone. A nude mouse xenografting system was also applied to detect in vivo sensitizing effects of HEPT. RESULTS: HEPT efficiently bound to HSP27 and showed sensitization after combined treatment with IR versus treatment with Cis alone in NCI-H1299 lung carcinoma cells, with higher HSP27 expression, which was similar to that of combined treatment with IR or with Cis alone in NCI-H460 lung carcinoma cells with lower HSP27 expression. In vivo image analysis using Cy5.5-labeled HEPT showed that HEPT was retained in HSP27-overexpressing cancer cells after xenografting to nude mice. Combined treatment of HEPT with IR versus that with Cis alone in xenografted mice showed that HEPT increased radio- or chemosensitization in NCI-H1299 cells compared to that in mice xenografted with NCI-H460 cells. CONCLUSIONS: The novel PKCδ-V5 HEPT may help overcome HSP27-mediated radio- or chemoresistance.
Authors:
Hae-June Lee; Eun-Ho Kim; Woo Duck Seo; Tae Hyun Choi; Gi-Jeong Cheon; Yoon-Jin Lee; Yun-Sil Lee
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-5
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  -     ISSN:  1879-355X     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 136-706, Korea.
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