Title:Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression in
Mice with Melanoma
Volume: 17
Author(s): Lirui Liang, Yang Li, Yang Jiao, Chunjing Zhang, Mingguang Shao, Hanyu Jiang, Zunge Wu, Haoqi Chen, Jiaming Guo, Huijie Jia*Tiesuo Zhao*
Affiliation:
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan
453000, P.R.China
- Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang,
Henan 453000, P.R.China
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R.China
- Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R.China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan
453000, P.R.China
- Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang,
Henan 453000, P.R.China
Keywords:
Maprotiline, Melanoma, PD-L1, Antitumour immune response, Tumor immunity, Mouse melanoma.
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.
