Heat shock protein 27-targeted heptapeptide of the PKCΔ catalytic V5 region sensitizes tumors with radio- and chemoresistance

Hae June Lee, Eun Ho Kim, Woo Duck Seo, Tae Hyun Choi, Gi Jeong Cheon, Yoon Jin Lee, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume80
Issue number1
DOIs
StatePublished - 1 May 2011

Keywords

  • HSP27
  • Heptapeptide
  • PKCδ-V5
  • Tumor sensitization

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