Deguelin Suppresses The Progression Of Gallbladder Carcinoma Cells Via Inhibition Of The PTEN/PI3K/Akt Pathway

Objective:To determine whether deguelin has antiproliferation and antimetastasis activities against gallbladder cancer.Materials and Methods:we cultured gallbladder carcinoma cells GBC-SD and SGC-996 and treated them with deguelin at three different concentrations(low-dose,12.5 uM;medium-dose,25 uM;high-dose,50uM).We detected the proliferation and apoptosis by Cell counting kit-8(CCK-8)assay and the annexin V-FITC/PI staining assay,and assessed the the ability of cell migration and invasion by wound healing assay and Transwell assay,and assessed the the ability of cell migration and invasion by wound healing assay and Transwell assay.The expression levels of epithelial-to-mesenchymal transition(EMT)markers and the involved signaling pathways were evaluated by western blot analysis.Morever,we built tumor xenografts in nude mice to further test the effects of deguelin on gallbladder cancer cell proliferation and metastasis.Results:We found that deguelin suppressed cell proliferation,migration and invasion in vitro and in vivo in dose-dependent manners.Deguelin decreased the expression level of p-AKT,N-cadherin and Vimentin.Meanwhile,deguelin increased the expression of PTEN,E-cadherin and zo-1Conclusions:Our findings suggest that deguelin significantly suppresses the migration and invasion of GBC cells through suppressing EMT and may be considered as a novel therapeutic agent for GBC.