Bufalin Exerts Inhibitory Effects on IL-1β-Mediated Proliferation and Induces Apoptosis in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes (Retracted article. See FEB, 2023)
Bufalin Exerts Inhibitory Effects on IL-1β-Mediated Proliferation and Induces Apoptosis in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes (Retracted article. See FEB, 2023)
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DOI：
10.1007/s10753-014-9882-5
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发表时间：
2014-10-01
期刊：
影响因子：
5.1
通讯作者：
Zhan, Hong-sheng
中科院分区：
文献类型：
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作者：
Chang, Yue-wen;Zhao, Yong-fang;Zhan, Hong-sheng
类风湿性关节炎成纤维细胞样滑膜细胞（RAFLSs）异常增殖并抵抗细胞凋亡。蟾蜍灵抑制人癌细胞增殖并诱导细胞凋亡。本研究探讨蟾蜍灵对白细胞介素-1 β（IL-1 β）诱导的RAFLS增殖和凋亡的影响。3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四氮唑溴化物法和Annexin V/碘化丙啶染色法分别检测细胞增殖和凋亡。蟾蜍灵剂量依赖性地抑制IL-1 β诱导的RAFLS增殖。从机制上讲，蟾蜍灵降低了丝裂原活化蛋白激酶（MAPK）和核因子-κ B（NF-κ B）的活化，这两者都参与了IL-1 β介导的RAFLS增殖。蟾蜍灵诱导RAFLSs细胞凋亡和线粒体损伤，这与Bcl-2下调、Bax上调、线粒体细胞色素c释放、caspase-3和聚ADP核糖聚合酶裂解增强有关。总之，我们的研究结果表明蟾蜍灵通过MAPK和NF-κ B信号通路抑制IL-1 β诱导的RAFLS增殖，并通过依赖于MAPK的通路诱导RAFLS凋亡。
Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1 beta)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1 beta-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappa B), both of which are involved in IL-1 beta-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1 beta-induced proliferation of RAFLSs through MAPK and NF-kappa B signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.