Department of Radiology, Case Western Reserve University , Cleveland, OH 44106-5056, USA.
Int J Hyperthermia. 2011;27(7):672-81. doi: 10.3109/02656736.2011.608218.
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.
Rat colorectal carcinoma cells were treated with low-grade hyperthermia (43°C) alone or in combination with Pluronics L10 (3 mg/mL), L61 (0.3 mg/mL), or L64 (0.5 mg/mL) for 20 min. 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 (10 mg/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.
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 9 h 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 5 h after hyperthermia in BDIX rat tumour models and no Hsp70 expression was observed in L61 pre-treated and control groups.
Pluronic effectively improves hyperthermic and low-grade hyperthermic treatment in part due to reduction of Hsp70 expression.
本研究旨在评估实验性结直肠癌模型中先前证明的嵌段共聚物 Pluronic 的热致敏作用与热休克蛋白 70（Hsp70）表达之间的关系，这种关系在体外和体内都得到了体现。
将大鼠结直肠癌细胞用低强度热疗（43°C）单独或与 Pluronic L10（3mg/mL）、L61（0.3mg/mL）或 L64（0.5mg/mL）联合处理 20 分钟。用标准测定法测定三磷酸腺苷（ATP）水平和细胞活力。用 Western blot 定量测定用上述剂量的 L10、L61 和 L64 以及单独和与热联合使用的 Pluronic P85（10mg/mL）处理的细胞中 Hsp70 的表达。使用具有侧腹肿瘤的 BDIX 大鼠研究 L61 和热疗对体内 Hsp70 表达的影响。
在体外，用 L10、L61 和 L64 加低强度热疗处理后，24 小时后 ATP 水平降至未处理对照的 8%至 66%。单独热疗后 9 小时观察到 Hsp70 表达的最大值。低强度热疗和 Pluronic 联合治疗最多可将 Hsp70 表达减少 6 小时，L10 似乎完全抑制了 Hsp70 表达。在体内，BDIX 大鼠肿瘤模型中热疗后 5 小时 Hsp70 表达增加，而在 L61 预处理和对照组中未观察到 Hsp70 表达。
Pluronic 通过降低 Hsp70 表达，有效改善高热和低热治疗效果。
