Li Xiaodong, Chen Jie, Zhang Riyi, Zou Songyan, Yang Dongdong, Tu Wei, Xie Fuyi, Mu Yinyu
Department of Clinical Laboratory, The Affiliated Li Huili Hospital, Ningbo University, 57 Xingning Road, Ningbo, 315000, China.
Ningbo University Health Science Center, 818 Fenghua Road, Ningbo, 315211, China.
Ann Hematol. 2025 Sep 2. doi: 10.1007/s00277-025-06571-z.
T-cell lymphoma (TCL) is a prevalent malignancy characterized by the aberrant proliferation of T cells. The molecular mechanism underlying TCL remains poorly understood, and effective therapeutic strategies are still limited. Maprotiline, a highly selective norepinephrine reuptake blocker, is primarily used in the treatment of various types of depression. Intriguingly, its potential therapeutic utility and underlying mechanisms in TCL have not been previously explored. In this study, we demonstrated for the first time that maprotiline significantly inhibits proliferation and migration while promoting apoptosis in TCL cells. Furthermore, in vivo experiments using TCL xenograft mouse models revealed that maprotiline treatment effectively suppresses tumor progression while maintaining a favorable safety profile with minimal toxicity. Mechanistically, our findings reveal that maprotiline exerts its anti-tumor effect by regulating the AKT/mTOR signaling pathway in TCL. Notably, we discovered that maprotiline substantially enhances the sensitivity of TCL cells to histone deacetylase inhibitor, thereby unveiling a promising combination therapeutic strategy for TCL treatment. These findings not only expand our understanding of maprotiline's pharmacological potential beyond its conventional antidepressant use, but also provide a novel therapeutic avenue for addressing the clinical challenges in TCL management.
T细胞淋巴瘤（TCL）是一种以T细胞异常增殖为特征的常见恶性肿瘤。TCL的分子机制仍知之甚少，有效的治疗策略也仍然有限。马普替林是一种高度选择性的去甲肾上腺素再摄取阻滞剂，主要用于治疗各种类型的抑郁症。有趣的是，其在TCL中的潜在治疗效用和潜在机制此前尚未被探索。在本研究中，我们首次证明马普替林显著抑制TCL细胞的增殖和迁移，同时促进其凋亡。此外，使用TCL异种移植小鼠模型进行的体内实验表明，马普替林治疗可有效抑制肿瘤进展，同时保持良好的安全性，毒性极小。从机制上讲，我们的研究结果表明，马普替林通过调节TCL中的AKT/mTOR信号通路发挥其抗肿瘤作用。值得注意的是，我们发现马普替林可显著增强TCL细胞对组蛋白去乙酰化酶抑制剂的敏感性，从而揭示了一种有前景的TCL联合治疗策略。这些发现不仅扩展了我们对马普替林药理学潜力的理解，超出了其传统抗抑郁用途，还为应对TCL治疗中的临床挑战提供了一条新的治疗途径。
