Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression in Mice with Melanoma.
Antitumour immune response
Maprotiline
Melanoma
Mouse melanoma.
PD-L1
Tumor immunity
Journal
Current molecular pharmacology
ISSN: 1874-4702
Titre abrégé: Curr Mol Pharmacol
Pays: United Arab Emirates
ID NLM: 101467997
Informations de publication
Date de publication:
2024
2024
Historique:
received:
09
06
2023
revised:
12
08
2023
accepted:
22
08
2023
medline:
27
11
2023
pubmed:
20
11
2023
entrez:
20
11
2023
Statut:
ppublish
Résumé
Research has revealed that the expression of PD-L1 is significantly upregulated in tumour cells and that the binding of programmed cell death protein 1 (PD-1) to programmed cell death 1 ligand 1 (PD-L1) inhibits the response of T cells, thereby suppressing tumour immunity. Therefore, blocking PD-L1/PD-1 signalling has become an important target in clinical immunotherapy. Some old drugs, namely, non-anticancer drugs, have also been found to have antitumour effects, and maprotiline is one of them. Maprotiline is a tetracyclic antidepressant that has been widely used to treat depression. However, it has not yet been reported whether maprotiline can exert an antitumour effect on melanoma. This study aimed to investigate the antitumour efficacy of maprotiline in mice with melanoma. In this study, female C57BL/6 mice were used to establish a tumour-bearing animal model. After treatment with maprotiline, the survival rate of mice was recorded daily. The expression of relevant proteins was detected by Western blotting, the proportion of immune cells was detected by flow cytometry, and the infiltration of immune cells in tumour tissue was detected by immunofluorescence staining. Maprotiline was found to inhibit the proliferation and migration of B16 cells while increasing cell apoptosis. Importantly, treatment with maprotiline decreased the expression of PD-L1 and increased the proportion of CD4+ T cells, CD8+ T cells, and NK cells in the spleen. It also increased the infiltration of CD4+ and CD8+ T cells in tumour tissue. Our research findings suggest that maprotiline enhances the antitumour immune response in mouse melanoma by inhibiting PD-L1 expression. This study may discover a new PD-L1 inhibitor, providing a novel therapeutic option for the clinical treatment of tumours.
Sections du résumé
BACKGROUND
BACKGROUND
Research has revealed that the expression of PD-L1 is significantly upregulated in tumour cells and that the binding of programmed cell death protein 1 (PD-1) to programmed cell death 1 ligand 1 (PD-L1) inhibits the response of T cells, thereby suppressing tumour immunity. Therefore, blocking PD-L1/PD-1 signalling has become an important target in clinical immunotherapy. Some old drugs, namely, non-anticancer drugs, have also been found to have antitumour effects, and maprotiline is one of them. Maprotiline is a tetracyclic antidepressant that has been widely used to treat depression. However, it has not yet been reported whether maprotiline can exert an antitumour effect on melanoma.
OBJECTIVE
OBJECTIVE
This study aimed to investigate the antitumour efficacy of maprotiline in mice with melanoma.
METHODS
METHODS
In this study, female C57BL/6 mice were used to establish a tumour-bearing animal model. After treatment with maprotiline, the survival rate of mice was recorded daily. The expression of relevant proteins was detected by Western blotting, the proportion of immune cells was detected by flow cytometry, and the infiltration of immune cells in tumour tissue was detected by immunofluorescence staining.
RESULTS
RESULTS
Maprotiline was found to inhibit the proliferation and migration of B16 cells while increasing cell apoptosis. Importantly, treatment with maprotiline decreased the expression of PD-L1 and increased the proportion of CD4+ T cells, CD8+ T cells, and NK cells in the spleen. It also increased the infiltration of CD4+ and CD8+ T cells in tumour tissue.
CONCLUSION
CONCLUSIONS
Our research findings suggest that maprotiline enhances the antitumour immune response in mouse melanoma by inhibiting PD-L1 expression. This study may discover a new PD-L1 inhibitor, providing a novel therapeutic option for the clinical treatment of tumours.
Identifiants
pubmed: 37982288
pii: CMP-EPUB-135227
doi: 10.2174/0118761429259562230925055749
doi:
Substances chimiques
B7-H1 Antigen
0
Maprotiline
2U1W68TROF
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e18761429259562Subventions
Organisme : Doctor Launch Fund of Xinxiang Medical University
ID : 505017, 505016
Organisme : Key Projects of Scientific Research for Higher Education of Henan Province
ID : 21A310012
Organisme : Young Backbone Teacher Training Projects of Universities in Henan province
ID : 2020GGJS149
Organisme : Science and Technology Research Project of Henan Province
ID : 222102310016
Organisme : Graduate Student Innovation Support Plan
ID : YJSCX202210Z
Organisme : Medical Science and Technology Research Program of Henan Province
ID : LHGJ20210388
Informations de copyright
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