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铁螯合剂与外源性光敏剂。通过氧化应激基因表达实现协同作用。

Iron Chelators and Exogenic Photosensitizers. Synergy through Oxidative Stress Gene Expression.

作者信息

Mrozek-Wilczkiewicz Anna, Malarz Katarzyna, Rams-Baron Marzena, Serda Maciej, Bauer Daniela, Montforts Franz-Peter, Ratuszna Alicja, Burley Thomas, Polanski Jaroslaw, Musiol Robert

机构信息

A. Chełkowski Institute of Physics, University of Silesia in Katowice, Poland.

Silesian Center for Education and Interdisciplinary Research, University of Silesia in Katowice, Chorzów, Poland.

出版信息

J Cancer. 2017 Jul 5;8(11):1979-1987. doi: 10.7150/jca.17959. eCollection 2017.

DOI:10.7150/jca.17959
PMID:28819397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5559958/
Abstract

In non-invasive anticancer photodynamic therapy (PDT), a nontoxic photosensitizer (PS), which is activated by visible light, is used as a magic bullet that selectively destroys cancer cells. Recently, we described the combined therapy of 5-aminolevulinic acid (ALA-PDT) with thiosemicarbazone (TSC), i.e. an iron-chelating agent. This resulted in a strong synergistic effect. Herein, we investigated a novel strategy using a combination of PDT consist of the xenobiotic-porphyrin type PS with TSC. We observed a synergistic effect for all of the pairs of TSC-PS. This approach can be rationalized by the fact that both chlorin and TSC can affect the generation of reactive oxygen species (ROS). In order to elucidate the plausible mechanism of action, we also combined the investigated PSs with DFO, which forms complexes that are redox inactive. We detected a slight antagonism or additivity for this combination. This may suggest that the ability of an iron chelator (IC) to participate in the production of ROS and the generation of oxidative stress is important.

摘要

在非侵入性抗癌光动力疗法(PDT)中,一种由可见光激活的无毒光敏剂(PS)被用作选择性破坏癌细胞的神奇子弹。最近,我们描述了5-氨基乙酰丙酸(ALA-PDT)与硫代卡巴腙(TSC)(一种铁螯合剂)的联合疗法。这产生了强烈的协同效应。在此,我们研究了一种使用由异生物质卟啉型PS与TSC组成的PDT组合的新策略。我们观察到所有TSC-PS对都有协同效应。这种方法可以通过二氢卟吩和TSC都能影响活性氧(ROS)的产生这一事实来解释。为了阐明可能的作用机制,我们还将研究的PS与DFO结合,DFO形成氧化还原无活性的复合物。我们检测到这种组合有轻微的拮抗作用或相加作用。这可能表明铁螯合剂(IC)参与ROS产生和氧化应激生成的能力很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/b86a71d53e45/jcav08p1979g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/1518e8961960/jcav08p1979g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/6806d9194e34/jcav08p1979g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/e1a28b57d7b9/jcav08p1979g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/3163b630223d/jcav08p1979g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/b86a71d53e45/jcav08p1979g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/1518e8961960/jcav08p1979g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/6806d9194e34/jcav08p1979g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/e1a28b57d7b9/jcav08p1979g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/3163b630223d/jcav08p1979g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/5559958/b86a71d53e45/jcav08p1979g005.jpg

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