Hu Hongzhi, Wang Shangyu, Shi Deyao, Zhong Binglong, Huang Xin, Shi Chunwei, Shao Zengwu
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
Onco Targets Ther. 2019 Jul 8;12:5377-5388. doi: 10.2147/OTT.S202026. eCollection 2019.
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. The purpose of this study was to examine the effect of lycorine on human OS and elucidated it underlying mechanisms 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. 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. 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.
石蒜碱是一种天然生物碱，已被证明具有多种生理作用，包括潜在的抗癌作用。然而，石蒜碱对骨肉瘤（OS）的抗癌作用及其具体分子机制仍不清楚。本研究旨在探讨石蒜碱对人骨肉瘤的作用并阐明其潜在机制。在体外实验中，用不同浓度的石蒜碱处理骨肉瘤细胞。然后检测细胞增殖、集落形成、细胞周期分布、凋亡、迁移和侵袭，以检测石蒜碱对骨肉瘤细胞系的抗癌作用。采用蛋白质免疫印迹分析来验证相关蛋白的表达。此外，还建立了小鼠异种移植模型来评估石蒜碱在体内对骨肉瘤的治疗潜力。体外实验结果表明，石蒜碱通过增强含SH2结构域的磷酸酶1（SHP-1）的表达和下调信号转导与转录激活因子3（STAT3）靶蛋白的表达，抑制组成型STAT3激活，从而诱导细胞凋亡和细胞周期阻滞，并抑制迁移和侵袭。此外，我们的小鼠异种移植模型显示石蒜碱在体内抑制肿瘤生长。这些结果表明，石蒜碱的抗骨肉瘤作用至少部分归因于对Janus激酶2/信号转导与转录激活因子3（JAK2）/STAT3通路的抑制。综上所述，这些结果表明石蒜碱有潜力成为未来人类骨肉瘤临床治疗中有前景的候选药物。
