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WHO I 脑膜瘤细胞对 5-氨基酮戊酸光动力疗法的敏感性与亚铁螯合酶活性相对应。

Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity.

机构信息

Department of Neurosurgery, University Hospital Schleswig Holstein, Campus Kiel, Germany.

出版信息

Photochem Photobiol. 2011 Jan-Feb;87(1):235-41. doi: 10.1111/j.1751-1097.2010.00821.x. Epub 2010 Nov 12.

Abstract

5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX), which can be used as a photosensitizer in photodynamic therapy (PDT). Accumulation of PpIX in benign meningioma cells has been observed previously, its exploitation for PDT, however, was discouraged by inconsistent results. To evaluate PDT for benign meningiomas, we investigated PpIX synthesis in two human meningioma cell lines (HBL-52 and BEN-MEN-1), their respective extracellular loss of PpIX and corresponding ferrochelatase (FECH) activity as well as their susceptibility to PDT. We demonstrated PpIX production after 5-ALA administration and minor loss to the extracellular space in both cell lines. However, significantly more (up to five times) PpIX was accumulated in BEN-MEN-1 as compared with HBL-52 cells. FECH activity was 2.7-fold higher in HBL-52 compared with BEN-MEN-1 cells and accordingly higher FECH levels could be shown in HBL-52 cells by Western blot analysis. BEN-MEN-1 cells were much more sensitive to PDT and cells could be almost completely killed by irradiation doses of 2 J cm(-2) , whereas HBL-52 showed only an insufficient response at this irradiation dose. We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.

摘要

5-氨基酮戊酸(5-ALA)是原卟啉 IX(PpIX)的天然前体,可作为光动力疗法(PDT)中的光敏剂。先前已经观察到良性脑膜瘤细胞中 PpIX 的积累,但其在 PDT 中的应用因结果不一致而受到阻碍。为了评估良性脑膜瘤的 PDT,我们研究了两种人脑膜瘤细胞系(HBL-52 和 BEN-MEN-1)中的 PpIX 合成、其各自的 PpIX 细胞外损失和相应的亚铁螯合酶(FECH)活性以及它们对 PDT 的敏感性。我们在两种细胞系中均证明了 5-ALA 给药后 PpIX 的产生和少量向细胞外空间的损失。然而,与 HBL-52 细胞相比,BEN-MEN-1 细胞中积累的 PpIX 明显更多(高达五倍)。与 BEN-MEN-1 细胞相比,HBL-52 细胞中的 FECH 活性高 2.7 倍,并且可以通过 Western blot 分析显示出 HBL-52 细胞中更高的 FECH 水平。BEN-MEN-1 细胞对 PDT 更敏感,照射剂量为 2 J cm(-2) 时几乎可以完全杀死细胞,而 HBL-52 细胞在该照射剂量下仅表现出不足的反应。我们得出结论,HBL-52 和 BEN-MEN-1 良性脑膜瘤细胞之间细胞内 PpIX 浓度的差异主要归因于 FECH 活性的差异,并且这些差异与它们对 5-ALA 诱导的 PDT 的敏感性相对应。

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