The effect of hypoxia on photodynamic therapy with 5-aminolevulinic acid in malignant gliomas.
Photodiagnosis Photodyn Ther
; 40: 103056, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35944845
ABSTRACT
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 ANDMETHODS:
Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups normoxia (O2 21%)-cultured cells (Normoxia-GSCs), and hypoxia (O2 5%)-cultured cells (Hypoxia-GSCs). To compare the effects of different oxygen partial pressures on photoporphyrin â ¨ (Ppâ ¨) biosynthetic activity, Ppâ ¨ biosynthetic enzyme and transporter expression levels were examined by qRT-PCR; the intracellular Ppâ ¨ concentration was determined using flow cytometry. Additionally, the sensitivity of these two groups of cells to ALA-PDT was evaluated in vitro.RESULTS:
Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert Ppâ ¨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of Ppâ ¨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs.CONCLUSION:
Hypoxia-GSCs had lower intracellular Ppâ ¨ 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 Ppâ ¨. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
/
Glioma
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article