MOP-dependent enhancement of methadone on the effectiveness of ALA-PDT for A172 cells by upregulating phosphorylated JNK and BCL2

Shi, Lei; Pohla, Heike; Buchner, Alexander; Zhang, Linglin; Pongratz, Thomas; Ruehm, Adrian; Zimmermann, Wolfgang; Gederaas, Odrun Arna; Wang, Xiuli; Stepp, Herbert und Sroka, Ronald (2020): MOP-dependent enhancement of methadone on the effectiveness of ALA-PDT for A172 cells by upregulating phosphorylated JNK and BCL2. In: Photodiagnosis and Photodynamic Therapy, Bd. 30, 101657

Abstract

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: 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: 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: 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1572-1000
• Sprache: Englisch