Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells.

Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells.
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分化增强了LNCAP前列腺癌细胞的氨基乙烯酸依赖性光动力治疗。

DOI:
10.1038/sj.bjc.6600575
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发表时间:
2002-11-18
影响因子:
8.8
通讯作者:
Hasan, T
Hasan, T
中科院分区:
医学1区
文献类型:
--
作者:
Ortel, B;Sharlin, D;O'Donnell, D;Sinha, AK;Maytin, EV;Hasan, T

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使用5-氨基乙酰丙酸(ALA)诱导的原卟啉IX(PpIX)的光动力疗法可应用于治疗各种器官中的肿瘤。为了增强现有的光动力治疗方案,我们研究了在光动力治疗中加入分化治疗对体外人前列腺癌细胞的影响。分化治疗本身的目的是使用药理学试剂逆转癌细胞中分化的缺乏。本研究的动机是利用一些血红素酶的分化依赖性表达来增强ALA-光动力疗法的肿瘤细胞毒性。在随后的ALA暴露期间,应用短疗程的分化疗法以增加PpIX形成。使用合成雄激素R1881、视黄酸的异构体和维生素D的类似物3至4天,LNCaP细胞中外源性ALA依赖性PpIX的形成增加,沿着生长停滞和分化的标记物。由于更高的PpIX水平,可见光暴露的细胞毒性作用也增强。短期分化治疗不仅增加了整体PpIX生产,但也减少了部分细胞含有低水平的PpIX的流式细胞术和荧光显微镜。这项研究表明,它将是可行的,以开发协议相结合的短期分化治疗与光动力治疗增强光敏化。英国癌症杂志(2002)87,1321-1327。www.bjcancer.com © 2002英国癌症研究中心
Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R1881, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with markers for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation. British Journal of Cancer (2002) 87, 1321–1327. doi:10.1038/sj.bjc.6600575 www.bjcancer.com © 2002 Cancer Research UK
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