Liu Haiyun, Liu Tingting, Zeng Junquan, Fang Quangang
Department of Clinical Laboratory, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nangchang, Jiangxi 330000, P.R. China.
Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nangchang, Jiangxi 330000, P.R. China.
Oncol Lett. 2025 Jul 4;30(3):426. doi: 10.3892/ol.2025.15172. eCollection 2025 Sep.
Multiple myeloma (MM) is a malignant tumor that originates in the plasma cells of the bone marrow, interfering with the production of healthy blood cells and causing notable damage to bones and other tissues. Currently, the treatment options for MM are limited and often fail to provide effective and well-tolerated solutions. Silymarin, a primary active compound found in the dried fruit of , is known for its inhibitory action on lipoxygenases and peroxidases. In addition to its known benefits in reducing liver toxicity and enhancing radiation protection, silymarin has shown promise in lowering lipid levels. Silymarin has anticancer properties; however, the specific mechanisms and efficacy of silymarin in treating MM require further investigation. In the present study, network pharmacology was employed to discern the targets and associated pathways of silymarin against MM. The cytotoxic effects of silymarin on MM were subsequently tested using RPMI 8226 and H929 cell lines. Furthermore, the molecular targets of silymarin in MM were assessed through immunofluorescence, reverse transcription-quantitative polymerase chain reaction and molecular docking studies. A total of 15 notable targets of silymarin associated with MM were identified, along with 60 interactions among these targets and several associated signaling pathways. experiments using Cell Counting Kit-8 and flow cytometry revealed that silymarin markedly promoted apoptosis in MM cells. Additionally, there was a reduction in the expression of anti-apoptotic genes, such as Bcl-2 and Bcl-xL. After silymarin treatment, a decrease in phosphorylation of JAK2 and STAT3 was observed in MM cells, and it was suggested that silymarin potentially binds to JAK2 and STAT3. In conclusion, silymarin was revealed to trigger apoptosis in MM cells by blocking the JAK2/STAT3 signaling pathway. This mechanism highlights the potential of silymarin as a therapeutic agent that can target specific molecular pathways to combat MM.
多发性骨髓瘤（MM）是一种起源于骨髓浆细胞的恶性肿瘤，它会干扰健康血细胞的生成，并对骨骼和其他组织造成显著损害。目前，MM的治疗选择有限，且往往无法提供有效且耐受性良好的解决方案。水飞蓟素是在[此处原文缺失植物名称]干燥果实中发现的一种主要活性化合物，以其对脂氧合酶和过氧化物酶的抑制作用而闻名。除了在降低肝毒性和增强辐射防护方面的已知益处外，水飞蓟素在降低血脂水平方面也显示出前景。水飞蓟素具有抗癌特性；然而，水飞蓟素治疗MM的具体机制和疗效需要进一步研究。在本研究中，采用网络药理学来识别水飞蓟素抗MM的靶点和相关途径。随后使用RPMI 8226和H929细胞系测试了水飞蓟素对MM的细胞毒性作用。此外，通过免疫荧光、逆转录定量聚合酶链反应和分子对接研究评估了水飞蓟素在MM中的分子靶点。共鉴定出15个与MM相关的水飞蓟素显著靶点，以及这些靶点之间的60种相互作用和若干相关信号通路。使用细胞计数试剂盒 - 8和流式细胞术进行的实验表明水飞蓟素显著促进MM细胞凋亡。此外，抗凋亡基因如Bcl - 2和Bcl - xL的表达降低。水飞蓟素处理后，在MM细胞中观察到JAK2和STAT3磷酸化水平降低，提示水飞蓟素可能与JAK2和STAT3结合。总之，研究表明水飞蓟素通过阻断JAK2/STAT3信号通路触发MM细胞凋亡。这一机制突出了水飞蓟素作为一种能够靶向特定分子途径对抗MM的治疗剂的潜力。
