title: [Activation of Wnt/β-catenin pathway in NK cells by glycogen synthase kinase-3β inhibitor TWS119 promotes the expression of CD62L].
abstract: OBJECTIVE
  To investigate the effect of Wnt/β-catenin pathway activation by glycogen synthase kinase-3β inhibitor 4,6-disubstituted pyrrolopyrimidine (TWS119) on proliferation and phenotypic characteristics of human nature killer (NK) cells.
  
  
  METHODS
  The peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and added to the complete medium containing recombinant human interleukin-2 (rhIL-2) and human AB serum to isolate NK cells from PBMCs. After co-cultured with 0-8.0 μmol/L TWS119 for 72 hours, growth curve and Wnt/β-catenin activation of NK cells in each group were determined by CCK-8 and Western blotting. The CD107a and CD62L (L-selectin) expressions in the NK cells were detected using flow cytometry.
  
  
  RESULTS
  NK cells were amplified to (61.76 ± 3.74)% after human PBMCs were cultured for 10 days. The 0-2.0 μmol/L TWS119 could promote the growth of NK cells in a dose-dependent manner, and the proliferation rate gradually dropped when TWS119 was more than 2.0 μmol/L. 0-8.0 μmol/L TWS119 could activate Wnt/β-catenin pathway and up-regulate the expression of CD62L in a dose-dependent manner, but it decreased the expression of CD107a.
  
  
  CONCLUSIONS
  Human NK cells isolated from peripheral blood treated with TWS119 gave rise to early mature CD62L⁺ NK cells.
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Junquan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Leiqing
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Central Laboratory, No. 97th Hospital of PLA, Xuzhou 221004, China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Chen
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C547688:TWS 119; D051176:beta Catenin; D019041:L-Selectin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3