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光动力疗法联合电穿孔体外细胞毒性作用的评估

Evaluation of cytotoxic effect of photodynamic therapy in combination with electroporation in vitro.

作者信息

Labanauskiene J, Gehl J, Didziapetriene J

机构信息

Institute of Oncology, Vilnius University, Santariskiu 1, LT-08660 Vilnius, Lithuania.

出版信息

Bioelectrochemistry. 2007 Jan;70(1):78-82. doi: 10.1016/j.bioelechem.2006.03.009. Epub 2006 Apr 5.

DOI:10.1016/j.bioelechem.2006.03.009
PMID:16698325
Abstract

Under the influence of electric pulses cells undergo membrane electroporation (EP), which results in increased permeability of the membrane to exogenous compounds. EP is applied in oncology as a method to enhance delivery of anticancer drugs. For that reason it was essential to combine photodynamic tumor therapy (PDT)--the cancer treatment method based on the use of photosensitizers that localize selectively in malignant tumors and become cytotoxic when exposed to light, and EP, with the aim to enhance the delivery of photosensitizers into the tumor and therefore to increase the efficacy of PDT. Thus, the aim of study was to evaluate the cytotoxic effect of PDT in combination with EP. A Chinese hamster lung fibroblast cell line (DC-3F) was used. The cells were affected by photosensitizers chlorin e(6) (C e(6)) at the dose of 10 mug/ml and aluminium phthalocyanine tetrasulfonate (AlPcS4) at the dose of 50 microg/ml. Immediately after adding of photosensitizers the cells were electroporated with 8 electric pulses at 1200 V/cm intensity, 0.1 ms duration, 1 Hz frequency. Then, after 20 min of incubation the cells were irradiated using a light source--a visible light passing through a filter (KC 14, emitted light from 660 nm). The fluence rate at the level of the cells was 3 mW/m(2). Cytotoxic effect on cells viability was evaluated using MTT assay. Our in vitro data showed that the cytotoxicity of PDT in combination with EP increases fourfold on the average. Based on the results we suggest that EP could enhance the effect of PDT.

摘要

在电脉冲的作用下,细胞会发生细胞膜电穿孔(EP),这会导致细胞膜对外源化合物的通透性增加。EP作为一种增强抗癌药物递送的方法应用于肿瘤学领域。因此,将光动力肿瘤治疗(PDT)——一种基于使用光敏剂的癌症治疗方法,光敏剂选择性地定位于恶性肿瘤中并在光照下变得具有细胞毒性——与EP相结合至关重要,目的是增强光敏剂向肿瘤的递送,从而提高PDT的疗效。因此,本研究的目的是评估PDT联合EP的细胞毒性作用。使用了中国仓鼠肺成纤维细胞系(DC - 3F)。细胞分别受到剂量为10微克/毫升的二氢卟吩e6(Ce(6))和剂量为50微克/毫升的四磺酸铝酞菁(AlPcS4)这两种光敏剂的作用。在加入光敏剂后,立即对细胞施加8个电脉冲,强度为1200伏/厘米,持续时间为0.1毫秒,频率为1赫兹。然后,在孵育20分钟后,使用光源——通过滤光片(KC 14,发射660纳米的可见光)的可见光对细胞进行照射。细胞水平的光通量率为3毫瓦/平方米。使用MTT法评估对细胞活力的细胞毒性作用。我们的体外数据表明,PDT联合EP的细胞毒性平均增加了四倍。基于这些结果,我们认为EP可以增强PDT的效果。

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