Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner.
- Author:
Yue SUN
1
;
Da-Wei YE
2
;
Peng ZHANG
1
;
Ying-Xing WU
3
;
Bang-Yan WANG
1
;
Guang PENG
1
;
Shi-Ying YU
1
Author Information
1. Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
2. Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China. dy0711@gmail.com.
3. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Publication Type:Journal Article
- Keywords:
bone destruction;
bone metastasis;
cytokines;
iguratimod;
nuclear factor-κB
- MeSH:
Animals;
Apoptosis;
drug effects;
Bone Neoplasms;
complications;
drug therapy;
pathology;
secondary;
Bone Resorption;
complications;
drug therapy;
pathology;
Breast Neoplasms;
complications;
drug therapy;
genetics;
pathology;
Carcinogenesis;
drug effects;
Cell Movement;
drug effects;
Cell Proliferation;
drug effects;
Chromones;
administration & dosage;
Female;
Humans;
Interleukin-6;
biosynthesis;
genetics;
MCF-7 Cells;
Neoplasm Invasiveness;
genetics;
pathology;
Rats;
Sulfonamides;
administration & dosage;
Transcription Factor RelA;
biosynthesis;
genetics
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2016;36(5):691-699
- CountryChina
- Language:English
-
Abstract:
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/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-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.
