The effect of hypoxia on photodynamic therapy with 5-aminolevulinic acid in malignant gliomas.
Aminolevulinic acid
Glioma stem cell
Hypoxia
Malignant glioma
Photodynamic therapy
Protoporphyrin-ⅸ
Journal
Photodiagnosis and photodynamic therapy
ISSN: 1873-1597
Titre abrégé: Photodiagnosis Photodyn Ther
Pays: Netherlands
ID NLM: 101226123
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
01
06
2022
revised:
24
07
2022
accepted:
05
08
2022
pubmed:
10
8
2022
medline:
15
12
2022
entrez:
9
8
2022
Statut:
ppublish
Résumé
Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT). Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs. Hypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.
Sections du résumé
BACKGROUND
BACKGROUND
Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT).
MATERIALS AND METHODS
METHODS
Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O
RESULTS
RESULTS
Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs.
CONCLUSION
CONCLUSIONS
Hypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.
Identifiants
pubmed: 35944845
pii: S1572-1000(22)00342-8
doi: 10.1016/j.pdpdt.2022.103056
pii:
doi:
Substances chimiques
Aminolevulinic Acid
88755TAZ87
Protoporphyrins
0
Oxygen
S88TT14065
Photosensitizing Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103056Informations de copyright
Copyright © 2022. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.