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.
Subject(s)
Animals , Female , Humans , Rats , Apoptosis , Bone Neoplasms , Drug Therapy , Pathology , Bone Resorption , Drug Therapy , Pathology , Breast Neoplasms , Drug Therapy , Genetics , Pathology , Carcinogenesis , Cell Movement , Cell Proliferation , Chromones , Interleukin-6 , Genetics , MCF-7 Cells , Neoplasm Invasiveness , Genetics , Pathology , Sulfonamides , Transcription Factor RelA , GeneticsABSTRACT
A collection of neurons in the upper lumbar spinal cord (lumbar segments 3 and 4) of male rats project to the lower lumbar spinal cord (lumbar segments 5 and 6) and release a gastrin-releasing peptide (GRP) to the somatic and autonomic regions, which are known to regulate male sexual reflexes. The GRP plays some special functions when bound to the specific GRP receptor (GRPR). The spinal GRP system is regulated by androgens. Accumulating evidence shows that GRP plays an important role in rat penile erection and ejaculation, and pharmacological stimulation of GRPRs with a specific agonist can restore penile reflexes and ejaculation in castrated male rats. Therefore, the GRP system appears to be a potential therapeutic target for the treatment of erectile dysfunction or ejaculatory dysfunction. The present paper briefly reviews the recent studies on the role of the spinal GRP system in regulating the sexual function of males.