title: Bone marrow mesenchymal stem cells from leukemia patients inhibit growth and apoptosis in serum-deprived K562 cells.
abstract: BACKGROUND
  The regulation of growth and apoptosis in K562 cells by human bone marrow mesenchymal stem cells (MSCs) from leukemia patients was investigated.
  
  
  METHODS
  K562 cells were cocultured with leukemic MSCs under serum deprivation. Cell Counting Kit-8 (CCK-8), PI staining, Annexin V/PI binding and FACS assays were used to investigate cell proliferation, cell cycle status, and apoptosis of K562 cells cultures in the presence or absence of 10% serum. Western blotting was used to determine the levels of Akt, phosphorylated Akt (p-Akt), the BCL-2 family member Bad, and phosphorylated Bad (p-Bad) proteins in K562 cells after coculturing with MSCs. The effects of LY294002 (a specific inhibitor of PI3K) on protein expression were also determined.
  
  
  RESULTS
  K562 cell proliferation was inhibited by coculture with MSCs and the dominant cell cycle was the G0-G1 phase. The proportion of apoptotic K562 cells was decreased and the levels of p-Akt and p-Bad were upregulated after exposing K562 cells to MSCs. However, when LY294002 was used, p-Akt and p-Bad proteins inK562 cells showed a significant reduction, while no distinct variation was seen in the nonphosphorylated Akt and Bad protein levels.
  
  
  CONCLUSIONS
  Leukemic MSCs can inhibit K562 cell expansion and modulate the cell cycle to a state of relative quiescence. This allows the K562 cells to endure adverse conditions such as serum starvation. The PI3K-Akt-Bad signaling pathway may be involved in this antiapoptotic process via phosphorylation of the Akt and Bad proteins. Blocking MSC-induced transduction of the PI3K-Akt-Bad pathway may be a potential strategy for a targeted therapy to combat leukemia.
authors.affiliation: The Affiliated Hospital, North China Coal Medical college, Tanshan, Heibei, 063000, PR China. john.semple@163.com
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wei
authors.forename: Naiyao
authors.initials: N
authors.lastname: Chen
authors.forename: Hongxing
authors.initials: H
authors.lastname: Guo
authors.forename: Xueming
authors.initials: X
authors.lastname: Wang
authors.forename: Fangyun
authors.initials: F
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: ShiHong
authors.initials: S
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism / Q000494:pharmacology; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: C494819:BAD protein, human; D016895:Culture Media, Serum-Free; D051034:Inhibitor of Apoptosis Proteins; D051025:bcl-Associated Death Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt