Evodiamine Inhibits the Progression of Esophageal Aquamous Cell Carcinoma via Modulating PI3K/AKT/mTOR Pathway

Abstract Purpose Esophageal squamous cell carcinoma (ESCC) is one of the main reasons of cancer-associated deaths. The effective antitumor drug evodiamine (EVO) is attracting increased, showing suppression of the development of tumor. Nevertheless, the potential mechanisms are not clear. Therefore, exploring promising therapeutic targets and the mechanisms of the anti-tumor effects of EVO is urgent for the treatment of ESCC. Methods In this study, two ESCC cell lines, TE-1 and KYSE150 were subjected to cell viability assay. Flow cytometry assays were applied to assess the apoptosis and the distribution of cell cycle. The metastasis capacity of ESCC cell was assessed via wound healing assays and transwell assays. Furthermore, western blot analysis is applied to test the expression of proteins. Finally, ESCC xenograft models were established in vivo. Results In the current research, we revealed that EVO triggered caspase-dependent apoptosis and G2/M phase arrest and impaired the migration and invasion, which suppressed the proliferation of ESCC cells. Mechanically, this study demonstrated that EVO could suppress the growth of ESCC cells by regulating PI3K/AKT/mTOR signal pathways. In addition, EVO treatment of mice also attenuated tumor growth in ESCC xenograft models. Conclusion: The results revealed that EVO induced ESCC cell apoptosis and blocked cell cycle at G2/M phase as well as anti-metastatic through suppressing PI3K/AKT/mTOR signal pathways, indicating EVO could be a potential chemotherapeutic candidate for ESCC.