title: [AG490 inhibits the proliferation of K562 and down-regulates protein phosphatase PHLPP expression].
abstract: This study was aimed to investigate the effect of AG490, a JAK2 inhibitor, on expression of PHLPP and p-Akt in K562. K562 cells were treated with different concentrations of AG490. The proliferation of K562 cells was examined by WST-1 assay and apoptosis of K562 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. The expressions of PHLPP, phosphorate-Akt (p-Akt) and total Akt protein were detected by Western blot. The results indicated that AG490 inhibited the proliferation of K562 cells in concentration-and time-dependent manners, with the IC(50) 338.0 µmol/L in 48 h. AG490 100 µmol/L also induced apoptosis of K562 cells in a time-dependent manner. AG490 100 µmol/L time-dependently down-regulated the protein expression of p-Akt and PHLPP, but without significant effect on expression of total Akt. It is concluded that AG490 can inhibit proliferation and induce apoptosis of K562 cells through down-regulation of p-Akt expression, but inhibiting efficacy of AG490 on K562 proliferation also may be limited due to the down-regulation of p-Akt regulatory protein PHLPP expression.
authors.affiliation: Department of Hematology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Chao-Qi
authors.initials: CQ
authors.lastname: Yan
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D006801:Humans; D020014:K562 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D009687:Nuclear Proteins; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases