Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner

作者：Sun, Yue; Ye, Da-wei^*; Zhang, Peng; Wu, Ying-xing; Wang, Bang-yan; Peng, Guang; Yu, Shi-ying^*

来源：Journal of Huazhong University of Science and Technology-Medical Sciences, 2016, 36(5): 691-699.

DOI：10.1007/s11596-016-1646-z

• iguratimod
• bone metastasis
• bone destruction
• cytokines
• nuclear factor-kappa B

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.

• 出版日期2016-10
• 单位华中科技大学