The Effects Of Lycorine On Proliferation, Invasion And Migration In Human Osteosarcoma And Its Molecular Mechanism

Objectives: Lycorine,a natural alkaloid,has been proved to possess various physiological effects,including the potential effect against cancer.However,the anticancer effect of Lycorine on osteosarcoma and detailed molecular mechanisms involved remained unclear.In this study,we investigated the role of Lycorine in the proliferation,invasion and migration of human osteosarcoma,and elucidated its potential role and molecular mechanism.Materials and Methods: In vitro assays,osteosarcoma 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 osteosarcoma 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 osteosarcoma in vivo.Results: The results in vitro demonstrated that Lycorin could significantly inhibit the proliferation,colony formation,migration and invasion of osteosarcoma cells,and induce cycle arrest and apoptosis.Western Blot results showed that Lycorin may suppress the expression of Janus kinase 2(JAK2)and signal transducers and activators of transcription 3(STAT3)through enhancing the expression of SH2 domain-containing phosphatase 1(SHP-1),thereby regulating the expression of target genes and related proteins downstream of STAT3.The results in vivo reaveled that Lycorin could significantly inhibit the growth of osteosarcoma in nude mice and had no obvious toxic and side effects on the important organs.Conclusions: The results demonstrated that anti-osteosarcoma effects of Lycorine due at least in part to the suppression of JAK2/STAT3 pathway.Besides,our study revealed that Lycorine exerted potent antitumor activity with low levels of toxicity invivo.Taken together,Lycorine possesses the potential to be a promising candidate in clinical therapy for human osteosarcoma in the future.