HEAT SHOCK PROTEIN 27-TARGETED HEPTAPEPTIDE OF THE PKC Delta CATALYTIC V5 REGION SENSITIZES TUMORS WITH RADIO- AND CHEMORESISTANCE
- Authors
- Lee, Hae-June; Kim, Eun-Ho; Seo, Woo Duck; Choi, Tae Hyun; Cheon, Gi-Jeong; Lee, Yoon-Jin; Lee, Yun-Sil
- Issue Date
- 1-5월-2011
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- Heptapeptide; HSP27; PKC delta-V5; Tumor sensitization
- Citation
- INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, v.80, no.1, pp.221 - 230
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
- Volume
- 80
- Number
- 1
- Start Page
- 221
- End Page
- 230
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/112475
- DOI
- 10.1016/j.ijrobp.2010.11.069
- ISSN
- 0360-3016
- Abstract
- Purpose: Previous data suggest that the PKC delta catalytic V5 (PKC delta-V5) heptapeptide (HEPT) (FEQFLDI) binds HSP27 and blocks HSP27-mediated radio- or chemoresistance. Here we investigated further the in vivo function of the PKC delta-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 PKC delta-V5 HEPT may help overcome HSP27-mediated radio- or chemoresistance. (C) 2011 Elsevier Inc.
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