Antitumor Effects of Berberine on Gliomas via Inactivation of Caspase-1-Mediated IL-1β and IL-18 Release
Antitumor Effects of Berberine on Gliomas via Inactivation of Caspase-1-Mediated IL-1β and IL-18 Release
复制标题
小檗碱通过灭活 Caspase-1 药物 IL-1β 和 IL-18 释放对胶质瘤的抗肿瘤作用
DOI：
10.3389/fonc.2019.00364
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发表时间：
2019-05-14
影响因子：
4.7
通讯作者：
Deng, Haoyu
中科院分区：
文献类型：
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作者：
Tong, Lei;Xie, Chuncheng;Deng, Haoyu
神经胶质瘤发生在脑或脊柱的神经胶质细胞中，是最普遍和最具破坏性的脑肿瘤类型。肿瘤免疫学的研究已经确立了肿瘤微环境作为肿瘤发生驱动因素的重要性。单核细胞释放的炎症介质如IL-1 β和IL-18调节恶性细胞生长所需的转录网络。小檗碱是一种天然植物生物碱，广泛存在于小檗属植物中。虽然它已被广泛用作抗肿瘤治疗在北美几十年来，我们的研究是第一次调查黄连素作为一种抗肿瘤剂在神经胶质瘤细胞。在这项研究中，我们证明，小檗碱显着抑制炎症细胞因子Caspase-1激活通过ERK 1/2信号和随后的生产IL-1 β和IL-18的胶质瘤细胞。此外，我们发现小檗碱处理导致U251和U87细胞运动性降低，随后细胞死亡。此外，我们的研究首次表明，小檗碱可以逆转上皮-间质转化的过程，这是肿瘤侵袭的标志。综上所述，我们的工作支持小檗碱作为一个假定的抗肿瘤剂靶向胶质瘤细胞。
Gliomas arise in the glial cells of the brain or spine and are the most prevalent and devastating type of brain tumors. Studies of tumor immunology have established the importance of the tumor micro-environment as a driver of oncogenesis. Inflammatory mediators such as IL-1 beta and IL-18 released by monocytes regulate transcriptional networks that are required for malignant cell growth. Berberine is a natural botanical alkaloid that is widely found in the Berberis species. Although it has been widely used as an anti-diarrheal treatment in North America for several decades, our study is the first to investigate berberine as an anti-tumor agent in glioma cells. In this study, we demonstrate that berberine significantly inhibits inflammatory cytokine Caspase-1 activation via ERK1/2 signaling and subsequent production of IL-1 beta and IL-18 by glioma cells. Moreover, we found that berberine treatment led to decreased motility and subsequently cell death in U251 and U87 cells. In addition, our study is the first to indicate that berberine can reverse the process of epithelial-mesenchymal transition, a marker of tumor invasion. Taken together, our work supports berberine as a putative anti-tumor agent targeting glioma cells.