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Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 691-699, 2016.
Article in English | WPRIM | ID: wpr-238457
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Sulfonamides / Bone Neoplasms / Bone Resorption / Breast Neoplasms / Cell Movement / Chromones / Interleukin-6 / Apoptosis / Cell Proliferation Type of study: Prognostic study Limits: Animals / Female / Humans Language: English Journal: Journal of Huazhong University of Science and Technology (Medical Sciences) Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Sulfonamides / Bone Neoplasms / Bone Resorption / Breast Neoplasms / Cell Movement / Chromones / Interleukin-6 / Apoptosis / Cell Proliferation Type of study: Prognostic study Limits: Animals / Female / Humans Language: English Journal: Journal of Huazhong University of Science and Technology (Medical Sciences) Year: 2016 Type: Article