Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner
Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner
复制标题
抗风湿药物艾拉莫德 (Iguatimod) (T-614) 通过以核因子-κ B 依赖性方式下调白细胞介素 6 的产生来减轻癌症引起的骨质破坏
DOI：
10.1007/s11596-016-1646-z
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发表时间：
2016-10-01
影响因子：
--
通讯作者：
Yu, Shi-ying
中科院分区：
文献类型：
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作者：
Sun, Yue;Ye, Da-wei;Yu, Shi-ying
据信细胞因子参与了骨转移中渐进相互作用的“恶性循环”。艾拉莫德是一种新型抗风湿药物，具有抗细胞因子的作用。在这项研究中，构建了大鼠模型来研究iguratimod对骨转移的影响，发现iguratimod减轻了癌症引起的骨破坏。为了进一步探索艾拉莫德的抗肿瘤活性是否有助于骨吸收抑制的效果，研究了两种人乳腺癌细胞系MDA-MB-231和MCF-7。CCK-8法和流式细胞术检测iguratimod对肿瘤增殖的影响。通过伤口愈合和Transwell测定来确定iguratimod对癌细胞的迁移和侵袭的影响。结果显示，高剂量（30 μ g/mL）的艾拉莫德轻微抑制癌细胞的增殖，但不能抑制其迁移和侵袭能力。有趣的是，iguratimod以浓度依赖性方式降低MDA-MB-231细胞中IL-6的转录水平。此外，iguratimod通过抑制NF-kappa B p65亚基的磷酸化而部分损害NF-kappa B信号传导。我们的研究结果表明，iguratimod可能通过NF-κ B依赖性方式部分降低IL-6的表达来减轻骨破坏，而对肿瘤增殖和侵袭几乎没有影响。
Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 mu g/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-kappa B signaling by suppressing the phosphorylation of NF-kappa B p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-kappa B-dependent manner, while it has little effect on the tumor proliferation and invasion.