• Lei Ning, Shuanglin Wan, Zhiwei Jie, Ziang Xie, Xiang Li, Xin Pan, Xinyu Wan, Wenxiang Chen, Hai Huang, Jiying Wang, An Qin, Shunwu Fan, and Xiangde Zhao.
• Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
• Spine. 2020 Feb 1; 45 (3): E126-E139.

Study DesignXenograft osteosarcoma mouse model.ObjectiveWe determined the effect of lycorine on osteosarcoma.Summary Of Background DataOsteosarcoma is an aggressive malignant neoplasm, is most prevalent in teenagers and adults and current treatment approaches have reached a survival plateau and attempts to improve osteosarcoma prognosis have proven unsuccessful. Thus there is clear evidence that development of new agents with high efficacy and fewer side effects to provide better prognostic outcome is urgently needed.MethodsThe toxicity, function and mechanism of lycorine (LY) on osteosarcoma were accessed in vitro by CCK-8 assay, flow cytometry, and western blotting and in vivo by the xenograft osteosarcoma mouse model.ResultsIn this study, we found that LY exhibited dose-dependent and time-dependent cytotoxic effects on human osteosarcoma cell-lines SJSA-1 and U2OS, inducing G1 phase cell cycle arrest and cellular death via apoptosis. Mechanistically, LY treatment elevated ROS generation that activates the p38 mitogen-activated protein kinases (MAPKs) and p53-dependent apoptotic program. Inhibition of ROS generation by NAC or p38 MAPK signaling by SB203580 attenuated the p53-mediated cell cycle arrest and apoptosis induced by LY. In vivo administration of LY markedly reduced tumor growth with little organ-related toxicity in a mouse xenograft model of osteosarcoma.ConclusionCollectively, our data suggests that LY exhibit therapeutic potential for the treatment of osteosarcoma.Level Of EvidenceN/A.

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