Preclinical evaluation of radiosensitizing activity of Pluronic block copolymers

Int J Radiat Biol. 2013 Oct;89(10):801-12. doi: 10.3109/09553002.2013.800246. Epub 2013 Jun 3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Mice
  • Poloxamer / chemistry*
  • Poloxamer / pharmacology*
  • Radiation-Sensitizing Agents / chemistry*
  • Radiation-Sensitizing Agents / pharmacology*
  • Stem Cells / drug effects
  • Stem Cells / radiation effects
  • Xenograft Model Antitumor Assays

Substances

  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Radiation-Sensitizing Agents
  • Poloxamer