Targeting mTOR by CZ415 Suppresses Cell Proliferation and Promotes Apoptosis via Lipin-1 in Cervical Cancer In Vitro and In Vivo.

摘要: CZ415, a novel inhibitor of mammalian target rapamycin (mTOR) kinase, has demonstrated anti-tumor activity in several types cancer. However, its biological function and underlying mechanism action cervical cancer (CC) have not been fully studied. Two CC cell lines (Hela Siha) were treated with increasing concentrations CZ415. Cell viability was tested the CCK-8 assay, proliferation determined by Edu staining colony formation apoptosis flow cytometry Hoechst 33342 staining. Protein expression evaluated western blotting. A nude mouse xenograft model used to confirm CZ415 vivo. Hematoxylin eosin (H&E) immunohistochemistry (IHC) performed on samples tumor tissue. Results showed that inhibited survival dose- time-dependent manner, 100 nanomolar 48 h optimal conditions. In vitro vivo experiments treatment significantly spheroid formation, proliferation, growth. Further studies anti-cancer effects due an induction apoptosis, which accompanied upregulation Bax downregulation Bcl-2 through Lipin-1. also reduced levels mTOR/STAT3 expression. these phenotypic changes reversed overexpression Our results suggest mTOR mediates malignancy via Lipin-1 might be useful for treating CC.