MOP-dependent enhancement of methadone on the effectiveness of ALA-PDT for A172 cells by upregulating phosphorylated JNK and BCL2.
ALA-PDT
Apoptosis
BCL2
Glioblastoma
JNK
MOP
Methadone
Journal
Photodiagnosis and photodynamic therapy
ISSN: 1873-1597
Titre abrégé: Photodiagnosis Photodyn Ther
Pays: Netherlands
ID NLM: 101226123
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
20
10
2019
revised:
30
12
2019
accepted:
10
01
2020
pubmed:
17
1
2020
medline:
15
5
2021
entrez:
17
1
2020
Statut:
ppublish
Résumé
Methadone, as a long-acting opioid analgesic, shows an ability to sensitize the treatment of ALA-PDT for glioblastoma cells (A172) in vitro by promoting apoptosis. However, the mechanisms how methadone enhances the effectiveness of ALA-PDT for tumor cells remains to be clarified. The expression of mu opioid receptor (MOP), apoptosis, phosphorylated c-Jun N-terminal kinase (JNK) and phosphorylated apoptosis regulator B cell lymphoma 2 (BCL2) were measured by flow cytometry. Cytotoxicity was determined using Cell Counting Kit-8 (CCK-8). A MOP antagonist, naloxone, was used to evaluate the role of MOP in the above process. It was found that A172 cells show the expression of MOP and that naloxone inhibits the enhancement of the methadone effect on apoptosis following ALA-PDT (p < 0.05). Phosphorylated JNK and BCL2 induced by ALA-PDT were promoted in the presence of methadone (p < 0.05). These methadone effects were also inhibited by naloxone (p < 0.05). The results suggest that apoptosis induced by ALA-PDT is enhanced by methadone, mostly MOP-mediated, through the upregulation of accumulation of phosphorylated JNK and BCL2, leading to a promotion of cytotoxicity of ALA-PDT for A172 cells.
Sections du résumé
BACKGROUND
BACKGROUND
Methadone, as a long-acting opioid analgesic, shows an ability to sensitize the treatment of ALA-PDT for glioblastoma cells (A172) in vitro by promoting apoptosis. However, the mechanisms how methadone enhances the effectiveness of ALA-PDT for tumor cells remains to be clarified.
METHODS
METHODS
The expression of mu opioid receptor (MOP), apoptosis, phosphorylated c-Jun N-terminal kinase (JNK) and phosphorylated apoptosis regulator B cell lymphoma 2 (BCL2) were measured by flow cytometry. Cytotoxicity was determined using Cell Counting Kit-8 (CCK-8). A MOP antagonist, naloxone, was used to evaluate the role of MOP in the above process.
RESULTS
RESULTS
It was found that A172 cells show the expression of MOP and that naloxone inhibits the enhancement of the methadone effect on apoptosis following ALA-PDT (p < 0.05). Phosphorylated JNK and BCL2 induced by ALA-PDT were promoted in the presence of methadone (p < 0.05). These methadone effects were also inhibited by naloxone (p < 0.05).
CONCLUSIONS
CONCLUSIONS
The results suggest that apoptosis induced by ALA-PDT is enhanced by methadone, mostly MOP-mediated, through the upregulation of accumulation of phosphorylated JNK and BCL2, leading to a promotion of cytotoxicity of ALA-PDT for A172 cells.
Identifiants
pubmed: 31945545
pii: S1572-1000(20)30009-0
doi: 10.1016/j.pdpdt.2020.101657
pii:
doi:
Substances chimiques
BCL2 protein, human
0
Photosensitizing Agents
0
Proto-Oncogene Proteins c-bcl-2
0
Receptors, Opioid, mu
0
Triazenes
0
1-phenyl-3,3-dimethyltriazene
79R3ZF226Y
Aminolevulinic Acid
88755TAZ87
MAP Kinase Kinase 4
EC 2.7.12.2
Methadone
UC6VBE7V1Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101657Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.