Bufalin attenuates cancer-induced pain and bone destruction in a model of bone cancer

Bufalin is a natural anti-inflammatory small molecule. Given the close relationship between inflammation and cancer, many scholars have studied the effect of bufalin on cancer in vitro, but in vivo research is still lacking. A murine bone cancer model was used in this study. We conducted pain sensitive test on mice with bone cancer, by nocifensive behavior, mechanical allodynia, and thermal hyperalgesia. Serum levels of bone loss markers with bufalin treatment were measured by ELISA. Expressions of osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) were analyzed in bufalin-treated mice by real-time PCR and Western blot. Cannabinoid 2 receptor (CB2) inverse agonist AM630 was administrated to mice with bone cancer together with bufalin. Bufalin relieved cancer-induced pain and bone destruction in the murine bone cancer model. Serum levels of bone loss markers after bufalin treatment were reduced. Bufalin upregulated OPG and downregulated RANKL. The CB2 receptor inverse agonist, AM630, reduced the pain relief of bufalin treatment in the mouse bone cancer model. This study demonstrates that bufalin relieves cancer-induced pain and bone destruction, which is mediated through the CB2 receptor.