MOP-dependent enhancement of methadone on the effectiveness of ALA-PDT for A172 cells by upregulating phosphorylated JNK and BCL2
| Autor: | Adrian Rühm, Herbert Stepp, Odrun A. Gederaas, Xiuli Wang, Wolfgang Zimmermann, Alexander Buchner, Ronald Sroka, Heike Pohla, Thomas Pongratz, Lei Shi, Linglin Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
MAP Kinase Kinase 4
Biophysics Receptors Opioid mu Apoptosis Dermatology (+)-Naloxone Pharmacology Flow cytometry Downregulation and upregulation Cell Line Tumor medicine Humans Pharmacology (medical) Phosphorylation Cytotoxicity Photosensitizing Agents medicine.diagnostic_test Apoptosis Regulator Kinase Chemistry Aminolevulinic Acid Oncology Photochemotherapy Proto-Oncogene Proteins c-bcl-2 Triazenes Methadone medicine.drug |
| Zdroj: | Photodiagnosis and photodynamic therapy. 30 |
| ISSN: | 1873-1597 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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