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Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

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

This study aimed to investigate the antitumour efficacy of maprotiline in mice with melanoma.

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

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

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.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2023-10-13
2024-11-22

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/content/journals/cmp/10.2174/0118761429259562230925055749
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Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression in Mice with Melanoma
Curr Mol Pharmacol 17, E18761429259562 (2024); https://doi.org/10.2174/0118761429259562230925055749
/content/journals/cmp/10.2174/0118761429259562230925055749
/content/journals/cmp/10.2174/0118761429259562230925055749
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  • Article Type:     Research Article
Keyword(s): Antitumour immune response; Maprotiline; Melanoma; Mouse melanoma; PD-L1; Tumor immunity

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