Time and dose dependence of pluronic bioactivity in hyperthermia-induced tumor cell death.
Time and dose dependence of pluronic bioactivity in hyperthermia-induced tumor cell death.
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DOI：
10.3181/0807-rm-223
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Exner AA
中科院分区：
文献类型：
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作者：
Krupka TM;Dremann D;Exner AA
Pluronic嵌段共聚物已显示使癌细胞敏化，导致抗癌剂的活性增加。在当前的研究中，我们研究了Pluronic生物活性在增强高血压诱导的癌细胞损伤中的新应用。将DHD/K12/TRb大鼠腺癌细胞暴露于43°C的低级别高温，有或没有Pluronic P85或Pluronic L 61。研究了一系列普朗尼克剂量、预暴露和热暴露持续时间，并优化了测试条件。通过测量细胞内ATP和线粒体脱氢酶活性来评估治疗效果。与单独的热或Pluronic相比，P85和L 61与热协同作用显著降低细胞活力。在最佳条件下，P85（10 mg/ml，240分钟）与15分钟热组合使细胞内ATP降低至对照的60.1 ± 3.5%，而单独热和不加热的P85分别引起ATP的可忽略不计的降低1.2%和3.8%。类似地，接受L 61（0.3mg/ml）预暴露120分钟的细胞显示细胞内ATP减少至对照的14.1 ± 2.1%。同样，单独加热或L 61预暴露导致细胞内ATP水平轻微降低（分别为1.5%和4.4%）。当通过线粒体酶活性评估生存力时，观察到可比较的结果。存活研究证实，活力的丧失转化为增殖活性的长期降低，特别是对于L 61处理的细胞。基于这些结果，我们得出结论，普朗尼克是有效的，在提高高温癌症治疗在体外增强热诱导的细胞毒性，在浓度和时间依赖性的方式。
Pluronic block copolymers have been shown to sensitize cancer cells resulting in an increased activity of antineoplastic agents. In the current study we examined a new application of Pluronic bioactivity in potentiating hyperthermia-induced cancer cell injury. DHD/K12/TRb rat adenocarcinoma cells were exposed to low-grade hyperthermia at 43°C with or without Pluronic P85 or Pluronic L61. A range of Pluronic doses, pre-exposure and heat exposure durations were investigated, and the test conditions were optimized. Treatment efficacy was assessed by measurement of intracellular ATP and mitochondrial dehydrogenase activity. Both P85 and L61 in synergy with heat reduced cell viability appreciably compared to either heat or Pluronic alone. Under optimal conditions, P85 (10 mg/ml, 240 mins) combined with 15 mins heat reduced intracellular ATP to 60.1 ± 3.5% of control, while heat alone and P85 without heat caused a negligible decrease in ATP of 1.2% and 3.8%, respectively. Similarly, cells receiving 120 mins pre-exposure of L61 (0.3 mg/ml) showed reduction in intracellular ATP to 14.1 ± 2.1% of control. Again, heat or L61 pre-exposure alone caused a minor decrease in levels of intracellular ATP (1.5% and 4.4%, respectively). Comparable results were observed when viability was assessed by mitochondrial enzyme activity. Survival studies confirmed that the loss of viability translates to a long-term reduction in proliferative activity, particularly for L61 treated cells. Based on these results, we conclude that Pluronic is effective in improving hyperthermic cancer treatment in vitro by potentiating heat-induced cytotoxicity in a concentration and time dependent manner.