Role of Pluronic block copolymers in modulation of heat shock protein 70 expression

Purpose: The goal of this study was to evaluate the relationship between previously demonstrated thermosensitising effects of the block copolymer, Pluronic, and heat shock protein 70 (Hsp70) expression in an experimental colorectal cancer model in vitro and in vivo. Materials and methods: Rat colorectal carcinoma cells were treated with low-grade hyperthermia (43°C) alone or in combination with Pluronics L10 (3mg/mL), L61 (0.3mg/mL), or L64 (0.5mg/mL) for 20min. Adinosine triphosphate (ATP) levels and cell viability were determined using standard assays. Hsp70 expression was quantified by western blot for cells treated with L10, L61, and L64 at doses specified above and Pluronic P85 (10mg/mL) alone and in combination with heat. BDIX rats with flank tumours were used to study the effect of L61 and hyperthermia on Hsp70 expression in vivo. Results: In vitro, treatment with L10, L61, and L64 plus low-grade hyperthermia lead to depletion of ATP levels to between 8 and 66% of untreated control after 24 h. Maximum expression of Hsp70 was observed at 9h following hyperthermia alone. The combination of low-grade hyperthermia and Pluronic treatment reduced Hsp70 expression for up to 6 hours, and L10 appeared to completely inhibit the Hsp70 expression. In vivo, Hsp70 expression was increased 5h after hyperthermia in BDIX rat tumour models and no Hsp70 expression was observed in L61 pre-treated and control groups. Conclusion: Pluronic effectively improves hyperthermic and low-grade hyperthermic treatment in part due to reduction of Hsp70 expression.