title: Matrine increases NKG2D ligand ULBP2 in K562 cells via inhibiting JAK/STAT3 pathway: a potential mechanism underlying the immunotherapy of matrine in leukemia.
abstract: OBJECTIVE
  The study aimed to investigate the role of the JAK/STAT3 pathway in the matrine induced ULBP2 expression on the human chronic myelogenous leukemia K562 cells.
  
  
  METHODS
  K562 cells were cultured, and the relevant mRNA expressions were detected.
  
  
  RESULTS
  Matrine induced the expression of four NKG2D ligands on K562 cells, of which ULBP2 had the highest increase. After treatment with 0.8 mg/mL matrine for 24 h, the mean fluorescence intensity (MFI) of ULBP2 increased. After matrine treatment, the sensitivity of K562 cells to NK cell-mediated killing increased significantly. After treatment with 0.2, 0.5 and 0.8 mg/ mL matrine, the percentage of K562 cells killed by NK cells was significantly higher than that of untreated cells (29.2%) (P<0.05). Matrine significantly inhibit the protein expression of phosphorylated STAT 3 and JAK2. Matrine markedly inhibited the IL-6 expression of K562 cells, and antagonized the IL-6 mediated STAT3 and JAK2 phosphorylation. In addition, matrine enhanced the inhibitory effect of STAT 3 inhibitor on STAT 3 activity. The silencing of STAT expression and inhibition of STAT3 activity significantly up-regulated the ULPB2 expression. Matrine had no effect on the expression of IL-6R and gp130 on K562 cells, the mRNA expression of IL-6R and gp130 increased slightly and the sgp 130 in cell supernatant significantly increased.
  
  
  CONCLUSIONS
  Our findings reveal IL-6 and IL-6 receptor-mediated JAK/STAT3 pathway is involved in the matrine induced up-regulation of NKG2D ligands ULBP2 on K562 cells. Matrine might inhibit IL-6 expression and then suppress the activation of IL-6 receptor-mediated JAK/STAT3 pathway.
authors.affiliation: Department of Hematology, Changzhou NO. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University Changzhou 213000, China.
authors.forename: Xuzhang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Laboratory Center, Changzhou NO. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University Changzhou 213000, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Laboratory Center, Changzhou NO. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University Changzhou 213000, China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Hematology, People Hospital of Jiangsu Province, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Hematology, Changzhou NO. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University Changzhou 213000, China.
authors.forename: Zhuxia
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Hematology, People Hospital of Jiangsu Province, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Sixuan
authors.initials: S
authors.lastname: Qian
authors.affiliation: Department of Hematology, People Hospital of Jiangsu Province, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Huizhou NO. 3 People's Hospital, Affiliated Hospital of Guangzhou Medical University Huizhou 615000, China.
authors.forename: Lingdi
authors.initials: L
authors.lastname: Ma
keywords: IL-6; K562 cells; Matrine; NK cells; NKG2D ligand; STAT3