Department of Orthopaedy, Yidu Central Hospital of Weifang, No. 4138 Linglongshan South Road, Weifang, 262500, China.
Department of Anesthesiology, Central hospital of Zibo Mining Group, No. 133 Zikuang Road, Zibo, Shandong, 255120, China.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Dec;390(12):1211-1219. doi: 10.1007/s00210-017-1419-7. Epub 2017 Aug 24.
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.
蟾毒灵是一种天然的抗炎小分子。鉴于炎症与癌症之间的密切关系，许多学者已经研究了蟾毒灵在体外对癌症的作用，但体内研究仍然缺乏。本研究采用了一种鼠骨肉瘤模型。我们通过伤害性行为、机械性痛觉过敏和热痛觉过敏对患有骨肉瘤的小鼠进行了疼痛敏感测试。通过 ELISA 测量了用蟾毒灵处理后血清中骨丢失标志物的水平。通过实时 PCR 和 Western blot 分析了蟾毒灵处理小鼠中骨保护素 (OPG) 和核因子-κB 受体激活剂配体 (RANKL) 的表达。将大麻素 2 型受体 (CB2) 反向激动剂 AM630 与蟾毒灵一起施用于患有骨肉瘤的小鼠。蟾毒灵缓解了鼠骨肉瘤模型中的癌性疼痛和骨破坏。蟾毒灵治疗后血清中骨丢失标志物的水平降低。蟾毒灵上调了 OPG 并下调了 RANKL。CB2 受体反向激动剂 AM630 降低了蟾毒灵治疗在鼠骨肉瘤模型中的止痛作用。本研究表明，蟾毒灵通过 CB2 受体缓解了癌症引起的疼痛和骨破坏。
