Licochalcone A Induces Cells Apoptosis And Inhibits Epithelial-to-Mesenchymal Transition Via The Wnt/?-Catenin Signaling Pathway In Human Osteosarcoma In Vivo And Vitro

Background and Purpose: Osteosarcoma(OS)is the most common primary bone tumor in adolescents and accounts for about 3.4% of all childhood cancers.The overall incidence worldwide is about 3.4 per 1 million in Adolescence is the peak age of OS because of its rapid bone growth.Meanwhile,OS tend to occur in the long bones of the extremities.Surgery combined with chemotherapy is still the traditional treatment for patients with OS.Methotrexate,cisplatin,adriamycin and ifosfamide are the drugs for chemotherapy,while etoposide is the drug of choice for patients of OS with metastatic disease.Despite significant advances in the diagnosis and treatment of OS over the past decade,60-70% of patients show no improvement in survival.The 5-year survival rate of patients with localized tumors is about 50%,while that of patients with distant lung metastases is only about 15-20%.EMT is a prominent example of cellular plasticity in embryonic development and cancer progression,the process by which epithelial cells transform into stromal cells to acquire stromal characteristics.EMT is thought to be involved in slowing down apoptosis and enhancing aggressiveness.So,it is urgent to find a new and effective method for OS patients.Methods: In this study,we investigated the antitumor activity of LHA against human osteosarcoma cell lines.Cell proliferation was detected by CCK-8 kit assay and colonies formation test.The ability of cells to migrate and invade was evaluated by the wound-healing test and the Transwell test.Hoechst33342 staining and flow cytometric Annexin V/PI staining were performed to evaluate the effect of LHA on apoptosis of OS.Western blot was used to detect the expression of transfer-related proteins and Wnt/?-catenin associated proteins.Besides,the xenograft model of osteosarcoma mice was established to study the antitumor effect of LHA in vivo.Results: LHA inhibits the proliferation of U2 OS and 143 B cells.LHA prohibits proliferation,migration and invasion of osteosarcoma cells in a dose-dependent and time-dependent manner,and induces apoptosis of OS cells.In addition,Wnt/?-catenin signaling pathway is inhibited,leading to down-regulation of relative proteins such as ?-catenin,c-jun.Furthermore,LHA inhibits the progress of epithelial mesenchymal transformation(EMT),according to the expression of EMT related proteins(N-cadherin,E-cadherin,Snail and Slug).In mouse xenograft models,LHA treatment prevented against tumor growth and metastasis in vivo.Conclusion: LHA not only induces apoptosis of osteosarcoma cells in vitro,but also blocks the Wnt/?-catenin signaling pathway and epithelial mesenchymal transformation(EMT)progress.In addition,LHA inhibits tumor growth in vivo.It can be considered that LHA has a good application prospect as a chemotherapy drug for osteosarcoma.