Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression inMice with Melanoma

作者：Lirui Liang, Yang Li, Yang Jiao, Chunjing Zhang, Mingguang Shao, Hanyu Jiang, Zunge Wu, Haoqi Chen, Jiaming Guo, Huijie Jia, Tiesuo Zhao · 发表于：Current Molecular Pharmacology · 年份：2023 · DOI：10.2174/0118761429259562230925055749 · 被引用次数：19 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Cancer Immunotherapy and Biomarkers、Tryptophan and brain disorders

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 splee...