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：孙越 叶达伟 张鹏 吴颖星 王邦彦 彭广 于世英 

机构地区：[1]Cancer Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [2]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [3]Department of Clinical Cancer Prevention,The University of Texas MD Anderson Cancer Center

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2016年第5期691-699,共9页华中科技大学学报（医学英德文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.81372852 and 81202095)

摘　　要：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 μg/m L） 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-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.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 μg/m L） 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-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.

关 键 词：rheumatic T-614 Interleukin invasion regulating cytometry metastasis manner suppression destruction 

分 类 号：R96[医药卫生—药理学]