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亚铁螯合酶沉默增强基于 5-氨基酮戊酸的荧光和光动力治疗效果。

Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy.

机构信息

Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.

出版信息

Br J Cancer. 2011 Mar 1;104(5):798-807. doi: 10.1038/bjc.2011.12. Epub 2011 Feb 8.

DOI:10.1038/bjc.2011.12
PMID:21304523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3048207/
Abstract

BACKGROUND

Recurrence of glioma frequently occurs within the marginal area of the surgical cavity due to invading residual cells. 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection has been used as effective therapeutic modalities to improve discrimination of brain tumour margins and patient prognosis. However, the marginal areas of glioma usually show vague fluorescence, which makes tumour identification difficult, and the applicability of 5-ALA-based photodynamic therapy (PDT) is hampered by insufficient therapeutic efficacy in glioma tissues.

METHODS

To overcome these issues, we assessed the expression of ferrochelatase (FECH) gene, which encodes a key enzyme that catalyses the conversion of protoporphyrin IX (PpIX) to heme, in glioma surgical specimens and manipulated FECH in human glioma cell lines.

RESULTS

Prominent downregulation of FECH mRNA expression was found in glioblastoma tissues compared with normal brain tissues, suggesting that FECH is responsible for PpIX accumulation in glioblastoma cells. Depletion of FECH by small interference RNA enhanced PpIX fluorescence after exposure to 5-ALA concomitant with increased intracellular PpIX accumulation in glioma cells. Silencing of FECH caused marked growth inhibition and apoptosis induction by PDT in glioma cells.

CONCLUSION

These results suggest that knockdown of FECH is a potential approach to enhance PpIX fluorescent quality for optimising the subjective discrimination of vague fluorescence and improving the effect of 5-ALA-PDT.

摘要

背景

由于残留细胞的侵袭，神经胶质瘤常在手术腔的边缘区域复发。5-氨基酮戊酸（5-ALA）荧光引导切除已被用作有效治疗方式，以提高脑肿瘤边界的辨别能力和患者的预后。然而，神经胶质瘤的边缘区域通常显示出模糊的荧光，这使得肿瘤的识别变得困难，并且由于胶质瘤组织中光动力疗法（PDT）的疗效不足，5-ALA 为基础的 PDT 的适用性受到阻碍。

方法

为了克服这些问题，我们评估了编码催化原卟啉 IX（PpIX）转化为血红素的关键酶亚铁螯合酶（FECH）基因在神经胶质瘤手术标本中的表达，并在人神经胶质瘤细胞系中操纵 FECH。

结果

与正常脑组织相比，胶质母细胞瘤组织中 FECH mRNA 表达明显下调，表明 FECH 负责 PpIX 在胶质母细胞瘤细胞中的积累。用小干扰 RNA 耗竭 FECH 后，暴露于 5-ALA 时 PpIX 荧光增强，同时胶质瘤细胞内 PpIX 积累增加。FECH 沉默导致 PDT 诱导的胶质瘤细胞明显生长抑制和凋亡。

结论

这些结果表明，FECH 的敲低可能是一种增强 PpIX 荧光质量的潜在方法，可优化对模糊荧光的主观辨别，并提高 5-ALA-PDT 的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/015ce389c64f/bjc201112f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/3385bd72c082/bjc201112f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/d187e19b5005/bjc201112f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/ebdc662b5c8d/bjc201112f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/48ecbd6ca1b3/bjc201112f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/0f4fa40a8172/bjc201112f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/576e42df4cf1/bjc201112f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/015ce389c64f/bjc201112f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/3385bd72c082/bjc201112f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/d187e19b5005/bjc201112f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/ebdc662b5c8d/bjc201112f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/48ecbd6ca1b3/bjc201112f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/0f4fa40a8172/bjc201112f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/576e42df4cf1/bjc201112f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/3048207/015ce389c64f/bjc201112f7.jpg

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