Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts

Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts
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DOI:
10.1111/bjd.14509
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发表时间:
2016-09-01
影响因子:
10.3
通讯作者:
Jagdeo, J.
Jagdeo, J.
中科院分区:
医学1区
文献类型:
--
作者:
Mamalis, A.;Koo, E.;Jagdeo, J.

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光化性角化病(AKs)被普遍认为是浸润性鳞状细胞癌的常见前驱病变。光动力疗法(PDT)是一种常见的、办公室内、野外治疗AKS的方法。临床和实验室观察表明,温度调节可以影响光动力疗法的效果。目的在体外人皮肤成纤维细胞模型中,证明热光动力疗法增加了细胞的凋亡性,并探讨了活性氧自由基的作用机制。方法用特定浓度和控制温度的氨基乙酰丙酸(ALA)处理原代人皮肤成纤维细胞。结果在33℃~42℃温度范围内,L-1ALA作用下的热PDT可显著增加细胞总凋亡率和超氧阴离子ROS的生成,并呈温度依赖性。结论热PDT可通过增加细胞内超氧阴离子自由基的产生而显著增加细胞的死亡。
BackgroundActinic keratoses (AKs) are generally accepted as common precursor lesions to invasive squamous cell carcinoma. Photodynamic therapy (PDT) is a common, in-office, field therapy modality used in the treatment of AKs. Clinical and laboratory observations have demonstrated that temperature modulation can affect PDT efficacy.ObjectivesTo demonstrate thermal PDT increases apoptotic cell death, and to investigate the mechanistic role of reactive oxygen species (ROS) free radicals in an in vitro human skin fibroblast model.MethodsThis study was completed using commercially available primary human skin fibroblasts treated with aminolaevulinic acid (ALA) at specific concentrations and controlled temperatures. Cell death, apoptosis and superoxide ROS levels were quantified.ResultsWe found that thermal PDT with 05 mmol L-1 ALA resulted in significant temperature-dependent increases in total apoptosis and superoxide ROS generation between 33 degrees C and 42 degrees C.ConclusionsOur results indicate that thermal PDT significantly increases apoptotic cell death through increased generation of superoxide ROS in a temperature-dependent manner.