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 language | English (US) |
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Pages (from-to) | 801-812 |
Number of pages | 12 |
Journal | International Journal of Radiation Biology |
Volume | 89 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2013 |
Externally published | Yes |
Keywords
- Apoptosis
- DNA damage
- Heat shock protein
- Pluronic
- Radiation
ASJC Scopus subject areas
- Radiological and Ultrasound Technology
- Radiology Nuclear Medicine and imaging