Polyphyllin I induces pyroptosis in diffuse large B-cell lymphoma by activating the caspase-6/ZBP1/NLRP3 signaling pathway

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-09-29 DOI:10.1016/j.intimp.2025.115592

Yulian Liu , Mengyue Fan , Yuanxin Chen , Chuanmin Zhang , Lijuan Wang , Yao Fu

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引用次数: 0

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive and heterogeneous hematological malignancy of B-cell origin, commonly observe in clinical practice. Chemotherapy resistance poses a significant challenge to DLBCL treatment, necessitating novel therapies. Polyphyllin I (PPI) exhibits anticancer effects on various cancer cells, but its impact on DLBCL remains unclear. This study investigated the mechanism underlying PPI in treating DLBCL, specifically focusing on the caspase-6/ZBP1/NLRP3 pathway involved in pyroptosis and apoptosis. The role caspase-6 plays in regulating pyroptosis is unknown. We hypothesized PPI activates this pathway, triggering tumor cell death. Through both in vitro and in vivo experiments, we found that PPI significantly promoted DLBCL cell pyroptosis and apoptosis by activating the caspase-6/ZBP1/NLRP3 pathway. These findings suggest that the caspase-6 pathway has the potential to be developed as a novel treatment for DLBCL. Further research is needed to explore the clinical application of PPI in lymphoma treatment and its potential synergies with other drugs.

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Polyphyllin I通过激活caspase-6/ZBP1/NLRP3信号通路诱导弥漫性大b细胞淋巴瘤的焦亡。

弥漫性大b细胞淋巴瘤（DLBCL）是一种高度侵袭性和异质性的血液系统恶性肿瘤，起源于b细胞，在临床实践中很常见。化疗耐药是DLBCL治疗的重大挑战，需要新的治疗方法。多叶茶素I （Polyphyllin I， PPI）对多种癌细胞均有抗癌作用，但其对DLBCL的影响尚不清楚。本研究探讨了PPI治疗DLBCL的机制，特别关注了参与焦亡和凋亡的caspase-6/ZBP1/NLRP3通路。caspase-6在调节焦亡中的作用尚不清楚。我们假设PPI激活这一途径，引发肿瘤细胞死亡。通过体外和体内实验，我们发现PPI通过激活caspase-6/ZBP1/NLRP3通路，显著促进DLBCL细胞焦亡和凋亡。这些发现表明，caspase-6通路有可能成为DLBCL的一种新治疗方法。PPI在淋巴瘤治疗中的临床应用及其与其他药物的潜在协同作用有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.