患有弥漫性大B细胞淋巴瘤（DLBCL）的患者，特别是在初始化疗后出现复发时，结果不尽如人意。 Platycodin D（PD）是从桔梗（Jacq。）A. DC.的根中分离出的三萜皂甙，已经表现出强大的抗癌活性。然而，到目前为止，关于PD对恶性淋巴瘤的影响的信息仍然不可用。在本研究中，我们显示PD剂量依赖性地抑制了一系列建立的DLBCL细胞系，这些细胞系代表不同的分子亚型，且它们对PD的敏感性相当。 PD诱导线粒体功能障碍和随后的内在凋亡，如线粒体膜电位的丧失和Annexin V阳性细胞的百分比增加所示。在机械上，PD治疗降低了包括MCL-1，BCL-2和BCL-XL在内的抗凋亡蛋白的表达水平，同时上调了促凋亡蛋白BAK的表达水平，随后是PARP的裂解。此外，PD协同增强了BCL-2抑制剂venetoclax的细胞毒性。在SUDHL-4诱导的xenograft小鼠模型中，PD治疗显著抑制了肿瘤的生长，没有明显的副作用。因此，我们的结果为PD在淋巴瘤治疗中的作用提供了新的见解。Copyright © 2023 Elsevier Inc. Published by Elsevier Inc.

Patients with diffuse large B-cell lymphoma (DLBCL) have unsatisfactory outcomes especially when relapse occurs after initial chemotherapy. Platycodin D (PD), a triterpenoid saponin isolated from the root of Platycodon grandiflorum (Jacq.) A. DC., has demonstrated potent anti-cancer activities. So far, however, information regarding the effect of PD on malignant lymphoma remains unavailable. In the present study, we showed that PD dose-dependently inhibited the viability of a serial of established DLBCL cell lines representing different molecular subtypes, and their sensitivities to PD were comparable. Mitochondrial dysfunction and subsequent intrinsic apoptosis were induced by PD, as indicated by the loss of mitochondrial membrane potential and the increase in the percentage of Annexin Ⅴ positive cells. Mechanistically, PD treatment downregulated expression levels of anti-apoptotic proteins including MCL-1, BCL-2, and BCL-XL, while upregulated the expression level of pro-apoptotic protein BAK, followed by the cleavage of PARP. Moreover, PD synergistically enhanced the cytotoxicity of BCL-2 inhibitor venetoclax. In a SUDHL-4-derived xenograft mouse model, PD administration significantly constrained the tumor growth without obvious side effects. Therefore, our results provided new insights into the role of PD in lymphoma therapy.Copyright © 2023. Published by Elsevier Inc.