Constitutive overexpression of HSP-70 in thermal resistant tumor cells does not alter sensitivity to porphyrin-, chlorin-, or purpurin-mediated PDT
Constitutive overexpression of HSP-70 in thermal resistant tumor cells does not alter sensitivity to porphyrin-, chlorin-, or purpurin-mediated PDT
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DOI：
10.1002/jpp.322
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发表时间：
2001-02-01
影响因子：
1.5
通讯作者：
Gomer, CJ
中科院分区：
文献类型：
--
作者：
Rucker, N;Ferrario, A;Gomer, CJ
细胞表达的70 kDa的热休克蛋白（HSP-70）观察高温后，并与随后的加热的瞬时电阻。光动力疗法（PDT）介导的氧化应激也可以诱导包括HSP-70在内的多种基因的转录和翻译表达。然而，PDT介导的HSP-70表达可以作为光敏剂类型和孵育条件的函数而变化。在目前的研究中，我们使用了三种临床相关的光敏剂，卟啉（Photofrin），红紫素（SnET 2），和二氢卟酚（NPe 6），研究PDT介导的HSP-70的表达谱和光敏特性在亲代辐射诱导的纤维肉瘤细胞（RIF-1）和耐热RIF-I克隆。我们观察到使用SnET 2或NPe 6的体外PDT治疗诱导HSP-70表达，但使用Photofrin的相当PDT治疗没有导致HSP-70水平增加。我们还观察到，在父母和耐热细胞克隆的PDT敏感性是相似的每种光敏剂，而热敏感性显着降低组成型过表达HSP-70的RIF克隆。这些结果表明，可定义的差异可以存在于不同的光敏剂的PDT诱导的分子途径。我们的研究结果还表明，HSP-70的组成性过表达不调节PDT的光敏性，无论PDT治疗是否诱导HSP-70的表达。我们得出结论，HSP-70表达在细胞PDT光敏性中不起重要作用，版权所有（C）2001 John Wiley & Sons，Ltd.
Cellular expression of the 70 kDa heat shock protein (HSP-70) is observed following hyperthermia and is correlated with transient resistance to subsequent heating. Photodynamic therapy (PDT) mediated oxidative stress can also induce transcriptional and translational expression of a variety of genes including HSP-70. However, PDT-mediated HSP-70 expression can Vary as a function of photosensitizer type and incubation conditions. In the current study we used three clinically relevant photosensitizers, a porphyrin (Photofrin), a purpurin (SnET2), and a chlorin (NPe6), to examine PDT-mediated HSP-70 expression profiles and photosensitivity characteristics in parental radiation-induced fibrosarcoma cells (RIF-1) and in thermal resistant RIF-I clones. We observed that in vitro PDT treatments using either SnET2 or NPe6 induced HSP-70 expression but that comparable PDT treatments using Photofrin did not result in increased HSP-70 levels. We also observed that PDT sensitivity in parental and heat-resistant cell clones were similar for each photosensitizer while thermal sensitivity was significantly reduced in the RIF clones which constitutively overexpressed HSP-70. These results indicate that definable differences can exist in the molecular pathways induced by PDT for different photosensitizers. Our results also demonstrate that constitutive overexpression of HSP-70 does not modulate PDT photosensitivity regardless of whether PDT treatments induce HSP-70 expression. We conclude that HSP-70 expression does not play a significant role in cellular PDT photosensitivity, Copyright (C) 2001 John Wiley & Sons, Ltd.