Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model

The bone is one of the most common sites of metastasis in patients with Cancer. Current treatments for bone metastases include bisphosphonates, denosumab, non-steroidal anti-inflammatory drugs and analgesics, but each of them has certain limitations. Cytokines and mediators released from various cells in the bone microenvironment may drive a vicious cycle of osteolytic bone metastases. Iguratimod (T-614), a novel disease-modifying anti-rheumatic drug, has demonstrated therapeutic effects by suppressing the production of inflammatory cytokines in rats and patients with rheumatoid arthritis. Therefore, the current study evaluated the hypothesis that iguratimod may protect against cancer-induced bone pain and bone metastasis in a rat model. For this purpose, rats inoculated with Walker 256 cells were treated with iguratimod from days 11-17 post-surgery. Mechanical paw withdrawal thresholds and expression levels of phosphorylated extracellular signal-related kinase (PERK) and c-Fos in the spinal cord were investigated to detect changes in bone pain. Bone destruction levels were detected using X-rays, hematoxylin and eosin and tartrate-resistant Acid Phosphatase staining. The results revealed that mechanical paw withdrawal thresholds and the expression levels of PERK and c-Fos declined in a dose-dependent manner in rats treated with iguratimod, and bone destruction severity was also reduced. These findings may provide important new insights into the treatment of bone metastasis symptoms.