Lycorine induces cell death in MM by suppressing Janus Kinase/signal transducer and activator of transcription via inducing the expression of SOCS1
Lycorine induces cell death in MM by suppressing Janus Kinase/signal transducer and activator of transcription via inducing the expression of SOCS1
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Lycorine 通过诱导 SOCS1 的表达来抑制 Janus 激酶/信号转导器和转录激活剂，从而诱导 MM 细胞死亡
DOI：
10.1016/j.biopha.2016.10.069
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ma Yongyong
中科院分区：
文献类型：
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作者：
Jin Zhouxiang;Zhou Shujuan;Zhang Yu;Ye Haige;Jiang Songfu;Yu Kang;Ma Yongyong
尽管使用了新型的抗骨髓瘤药物，但几乎所有的患者最终都会复发或对药物治疗产生抗药性。治疗多发性骨髓瘤(MM)迫切需要新的、更有效的药物。JAK-STAT信号通路在骨髓瘤细胞的增殖中起重要作用。石蒜碱是从石蒜科植物中提取的一种天然生物碱，已显示出对多种实体瘤的抗肿瘤作用。在这项研究中，我们发现石蒜碱抑制了MM细胞系和来自我们四个MM患者的原代骨髓瘤细胞的细胞活力和诱导细胞死亡。研究表明，在石蒜碱治疗后，骨髓瘤细胞周期被阻止在G0/G1期。进一步的机制分析表明，石蒜碱通过上调骨髓瘤细胞和患者骨髓瘤细胞中SOCS1的表达来抑制JAK2/STAT信号转导。重要的是，我们发现HDAC8被敲除导致SOCS1表达增加。总之，我们的发现表明石蒜碱是一种有效的新型组蛋白脱乙酰酶抑制剂，并通过上调MM细胞中SOCS1的表达来抑制JAK2/STAT信号。
Despite the use of novel anti-myeloma agents,nearly all patients will eventually relapse or become refractory to drug treatment. New and more effective drugs for multiple myeloma (MM) are urgently needed. The JAK-STAT signaling pathway is important in the proliferation of myeloma cells.Lycorine,a natural alkaloid extracted from amaryllidaceae, has shown anti-tumor effects against a variety of solid tumors. However, its effects on MM remain unclear.In this study,we found that lycorine inhibited cellular viability and induced cell death in MM cell lines and primary myeloma cells which were derived from our four MM patients. The study showed that myeloma cells’ cycle was being arrested under the G0/G1 phase followed by the lycorine treatment. Further mechanism analysis demonstrated that lycorine inhibited JAK2/STAT signaling through upregulation of SOCS1 in MM cells and patient MM cells.Importantly, we found that knockdown of HDAC8 resulted in increased expression of SOCS1. Collectively, our findings suggested lycorine acted as a potent novel histone deacetylase inhibitor and inhibited JAK2/STAT signaling through upregulation of SOCS1 in MM cells.