OncoTargets and Therapy (Jul 2019)
Lycorine exerts antitumor activity against osteosarcoma cells in vitro and in vivo xenograft model through the JAK2/STAT3 pathway
Abstract
Hongzhi Hu,1,* Shangyu Wang,1,* Deyao Shi,1 Binglong Zhong,1 Xin Huang,1 Chunwei Shi,2 Zengwu Shao11Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 2Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China*These authors contributed equally to this workBackground: Lycorine, a natural alkaloid, has been indicated to have various physiological effects, including a potential effect against cancer. However, the anticancer effect of lycorine on osteosarcoma (OS) and the detailed molecular mechanisms involved remain unclear.Purpose: The purpose of this study was to examine the effect of lycorine on human OS and elucidated it underlying mechanismsMaterials and methods: In vitro assays, OS cells were treated with lycorine at various concentrations. Then the cell proliferation, colony formation, cell cycle distribution, apoptosis, migration and invasion were assayed to detect the anticancer effect of lycorine on OS cell lines. Western blotting analysis was used to verify the expression of related proteins. In addition, the mouse xenograft model was performed to evaluate lycorine’s therapeutic potential on OS in vivo.Results: The in vitro results demonstrated that lycorine induced apoptosis and cell cycle arrest and suppressed the migration and invasion by suppressing constitutive signal transducers and activators of transcription 3 (STAT3) activation through enhancing the expression of SH2 domain-containing phosphatase 1 (SHP-1) and downregulating the expression of STAT3 target proteins. Moreover, our mouse xenograft model revealed that lycorine inhibited the tumor growth in vivo.Conclusion: These results demonstrated that the anti-OS effects of lycorine were at least partly due to the suppression of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2)/STAT3 pathway. Taken together, these results indicate that lycorine possesses the potential to be a promising candidate in clinical therapy for human OS in the future.Keywords: lycorine, osteosarcoma, anticancer, SHP-1, JAK2/STAT3
