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Updated: Jul 10, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression in Mice with Melanoma
Lirui Liang1,2,3, Yang Li1,2,4, Yang Jiao1
1Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R.China.
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.
Insights
Maprotiline, an antidepressant, was found to inhibit melanoma growth in mice by reducing PD-L1 expression and boosting immune cell activity. This suggests maprotiline as a potential new cancer therapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are key regulators of tumor immunity.
- Inhibiting PD-1/PD-L1 signaling is a crucial strategy in cancer immunotherapy.
- Maprotiline, an established antidepressant, has shown potential as an anticancer agent.
Purpose of the Study:
- To investigate the antitumour efficacy of maprotiline in a mouse melanoma model.
- To determine if maprotiline affects PD-L1 expression and immune cell responses in melanoma.
Main Methods:
- Established a melanoma-bearing mouse model using C57BL/6 mice.
- Administered maprotiline and monitored survival rates.
- Analyzed protein expression (Western blotting), immune cell populations (flow cytometry), and immune cell infiltration (immunofluorescence).
Main Results:
- Maprotiline inhibited B16 melanoma cell proliferation and migration while increasing apoptosis.
- Maprotiline treatment reduced PD-L1 expression in tumors.
- Increased proportions of CD4+ T cells, CD8+ T cells, and NK cells were observed in the spleen, along with enhanced T cell infiltration into tumor tissue.
Conclusions:
- Maprotiline demonstrates antitumour effects in melanoma by enhancing the immune response through PD-L1 inhibition.
- Maprotiline represents a potential novel therapeutic agent for melanoma and possibly other cancers.
