Heat Shock Protein 27-Targeted Heptapeptide of the PKC{Delta} Catalytic V5 Region Sensitizes Tumors With Radio- and Chemoresistance
- Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 136-706 (Korea, Republic of)
- Department of Functional Crops, NICS, RDA, Miryang 627-803 (Korea, Republic of)
- Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 136-706 (Korea, Republic of)
- College of Pharmacy and Division of Life Science and Pharmaceuticals, Ewha Womans University, Seoul 120-750 (Korea, Republic of)
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.
- OSTI ID:
- 21491739
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 80, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2010.11.069; PII: S0360-3016(10)03697-7; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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