title: [Sorafenib induces apoptosis of U937 cells via inhibiting WNT signal pathway].
abstract: This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3β, β-catenin and cyclin-D1 were assayed by Western blot. The results showed that the proliferation of U937 cells was inhibited by sorafenib in a dose-dependent manner (p < 0.05). Sorafenib induced cell apoptosis and cell cycle G(1)/G(0) arrest. Compared with results of Western blot before treatment, expression of inactivated GSK-3β, β-catenin and Cyclin-D1 down-regulated in a dose-dependent manner after treatment with sorafenib, this same changes were observed after up-regulation of inactivated GSK-3β by LiCl (p < 0.05). It is concluded that sorafenib inhibits the proliferation of U937 cells and induces cell apoptosis through reducing negative regulation of WNT signal pathway on inactivated GSK-3β and down-regulating β-catenin and cyclin-D1 level, which result in U937 cell cycle G(1)/G(0) arrest.
authors.affiliation: Department of Hematology, Sun Yat-Sen University Third Hospital, Guangzhou, China. ruozhi_xiao@yahoo.com
authors.forename: Ruo-Zhi
authors.initials: RZ
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Li-Lin
authors.initials: LL
authors.lastname: Wang
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Ruan
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: He
authors.forename: Mu-Jun
authors.initials: MJ
authors.lastname: Xiong
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001557:Benzenesulfonates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib; D020298:U937 Cells; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001557:Benzenesulfonates; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D010671:Phenylurea Compounds; D011725:Pyridines; D051176:beta Catenin; D019938:Cyclin D1; D009536:Niacinamide; D000077157:Sorafenib; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3