Preclinical evaluation of radiosensitizing activity of Pluronic block copolymers

Reshani H. Perera, Ravi Patel, Hanping Wu, Mihika Gangolli, Bryan Traughber, Nancy Oleinick, Agata A. Exner

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Purpose: Pluronic block copolymers are non-ionic surfactants with demonstrated sensitizing activity in chemotherapy and hyperthermia in various tumor cell lines. In the current study we investigated the potential activity of Pluronic as a radiosensitizing agent. Materials and methods: As a possible mechanism, the effect of Pluronic on Hsp70 and Hsp90 was examined. Gli36 human glioma cells were treated with radiation alone as well as with a combination treatment of Pluronic and radiation. Results: Clonogenic cell survival assays show that Pluronic has an elevated effect on radiosensitization (50% high, p < 0.01), even with radiation doses as low as 2 Gy. The Hsp90 level was reduced 24 h after the combined treatment in both in vitro and in vivo. Similarly, Hsp70 levels were also decreased 24 h post treatment. When Gli36 cells were exposed to Pluronic before and during irradiation, DNA DSB: double-strand breaks repair was reduced, and elevated apoptosis was also seen in tumor xenografts. Conclusion: Data suggest the potential use of L10 as a radiosensitizer. While the mechanism of sensitization requires additional investigation, the presented results indicate that the effect may be due, in part, to a decrease in Hsp90 and 70 levels and increased DNA damage.

Original languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalInternational Journal of Radiation Biology
Volume89
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Apoptosis
  • DNA damage
  • Heat shock protein
  • Pluronic
  • Radiation

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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