Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy
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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.
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Genetic silencing of FECH significantly increases ALA-PpIX fluorescence in multiple cell lines and even in an animal study.
“Although genetic silencing of FECH significantly increases ALA-PpIX fluorescence in multiple cell lines [108,109,110,111] and even in an animal study [112], pharmacological inhibition of FECH with enzymatic inhibitors for the enhancement of PpIX has not been well studied.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [110]
Citation [112] is attached specifically to the animal-study claim. The Results section reports significantly increased ALA-PpIX fluorescence after FECH silencing in two glioma cell lines, but our copy does not report FECH-silencing fluorescence results from an animal study. The Discussion describes the silencing results as in vitro and notes limitations on applying siRNA in vivo (page unavailable). (LLM, conf=0.76)
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- Authors
- Teng, L., Nakada, M., Zhao, S.-G., Endo, Y., Furuyama, N., Nambu, E., Pyko, I. V., Hayashi, Y., & Hamada, J.-I.
- Affiliations
- Kanazawa University (JP)
- Harbin Medical University (CN)
- Corresponding author
- Nakada, M
- Venue
- British Journal of Cancer
- Published
- 2011-02-08
- Volume
- 104
- Issue
- 5
- Pages
- 798-807
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3048207
- OpenAlex
- W2050753593
- Cited by
- 172
- References
- 47
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 9 · 2023: 12 · 2022: 15 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 14 · 2015: 12 · 2014: 7 · 2013: 8 · 2012: 3
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Research Foundation for Clinical Pharmacology
- Foundation for Promotion of Cancer Research
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- ferrochelatase, 5-aminolevulinic acid, photodynamic therapy, fluorescence-guided surgery, glioma, glioblastoma, protoporphyrin IX, heme biosynthesis, gene silencing, siRNA, tumour margin delineation, apoptosis
- MeSH terms
- Aminolevulinic Acid, Ferrochelatase, Fluorescence, Glioma, Humans, Photochemotherapy, Protoporphyrins, Gene Silencing, Cell Line, Tumor
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