Abstract
ABSTRACTEpithelial ovarian cancer is prone to metastasizing at an early stage, but their mechanisms remain unclear. CRM1 is an important nuclear exportin and inhibitors targeting CRM1 has been explored as an anti-cancer strategy. In previous study, we observed that PEITC could combine with the hydrophobic pocket of CRM1. In this study, we focused on the effects of PEITC on EOC and its mechanisms. Results showed that IC50 values of PEITC on SKOV3 and HO8910 cell line were 42.14 μM and 37.29 μM, respectively. PEITC inhibits the migration and invasion of SKOV3 and HO8910 cells in vitro. Oral administration of 10 μmol PEITC suppressed the metastasis of EOC in a xenograft mouse model in vivo. PEITC treatment decreased the expressions of CRM1 and mTOR (cargo protein of CRM1) in EOC cell lines and in xenograft mouse tissues. Moreover, CRM1-mediated nuclear export was attenuated by PEITC, mTOR accumulated in nucleus, expressions of mTORS2448 and downstream effectors STAT3S727, MMP2 and MMP9 were decreased in a dose- and time-dependent manner. Furthermore, immunohistochemical analysis showed that CRM1 and mTOR were increased in EOC tissues compared with benign ovarian tumors, and related with advanced stage, type II EOC, positive peritoneal cytology and decreased overall survival. In addition, CRM1 was positively correlated with mTOR levels. In conclusion, our data demonstrated that PEITC suppresses the metastasis of EOC through inhibiting CRM1-mediated nuclear export, subsequently suppressing the mTOR-STAT3 pathway. Both CRM1 and mTOR were increased in EOC patients, providing a rationale for further clinical investigation of PEITC in EOC treatment.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.