Dezocine alleviates cancer-induced bone pain and suppresses intraosseous tumor growth in renal cell carcinoma via the NAMPT/NAD+ axis.

Bone metastasis-associated pain is a major cause of morbidity in advanced renal cell carcinoma (RCC), and effective therapies that concurrently mitigate pain and intraosseous tumor burden remain limited. Here, we evaluated dezocine as a potential dual-action agent and explored the involvement of the NAMPT/NAD+ axis. In 786-O cells, dezocine dose-dependently suppressed proliferation (IC50 = 73.6 μM), clonogenicity and increased apoptosis, accompanied by reduced NAMPT expression and a decreased NAD+/NADH ratio. Pharmacological rescue with the NAMPT activator SBI-797812 partially reversed these effects. In vivo, using an intra-tibial RCC cell inoculation model that recapitulates osteolysis and cancer-induced bone pain (CIBP), dezocine alleviated mechanical allodynia and thermal hyperalgesia, and reduced osteolytic bone destruction and intraosseous tumor progression; co-administration of SBI-797812 partially attenuated these effects (n = 6). Tumor tissues from dezocine-treated mice showed decreased Ki67 and NAMPT, increased cleaved caspase-3, and enhanced AMPK phosphorylation, consistent with metabolic stress-associated apoptosis. Collectively, these findings suggest that dezocine may provide dual analgesic and antitumor benefits in intraosseous RCC lesions, at least in part by suppressing the NAMPT/NAD+ axis, supporting further translational evaluation for bone metastasis-associated pain management.