title: [The induced differentiation and apoptosis of THP-1 cells by anti-CD44 antibody and its mechanism].
abstract: OBJECTIVE
  To investigate the effects of anti-CD44 mAb A3D8 on the cell proliferation of human acute monocytic leukemia cell line THP-1 and its mechanism.
  
  
  METHODS
  Cell proliferation was assayed with MTT method, the expression of CD33, CD15, CD11b, CD14, Annexin-V, caspase-3 and cell cycle with flow cytometry, and the expression of p-Akt, p-ERK, bcl-2 and p27kip1 with Western blot.
  
  
  RESULTS
  A3D8 could remarkably inhibit the proliferation capacity of the THP-1 cells in a dosage- and time-dependent manner. THP-1 differentiation was observed when treated with A3D8 (2.0 µg/ml) for one to six days. Expression of CD33 (68.9 ± 2.0 vs 39.3 ± 1.5), CD15 (61.7 ± 5.5 vs 12.9 ± 2.6), CD11b (67.3 ± 3.8 vs 14.0 ± 2.0) and CD14 (83.0 ± 5.7 vs 8.0 ± 1.0) was significantly increased at day 4 compared with the control group (all P < 0.01). Cell cycle of the THP-1 cells was arrested in G(0)/G(1). Expression of the Annexin-V \[(32.5 ± 2.5)% vs (2.4 ± 0.3)%\] and caspase-3 \[(33.3 ± 2.5)% vs (3.6 ± 0.3)%\] was much higher than that in normal controls (all P < 0.01), and apoptosis was observed in THP-1 cells at day 5. Expression of p-Akt (0.24 ± 0.06 vs 1.20 ± 0.15), p-ERK (0.32 ± 0.05 vs 1.24 ± 0.09), and bcl-2 (0.11 ± 0.05 vs 0.65 ± 0.07) was much lower than that of the controls (all P < 0.01), while p27kip1 (1.08 ± 0.09 vs 0.10 ± 0.02) was significantly increased at day 4 (P < 0.05).
  
  
  CONCLUSIONS
  Anti-CD44 antibody can induce the differentiation and apoptosis of THP-1 cell through inhibiting PI3K/AKt and ERK1/2 signaling pathway.
authors.affiliation: Central Laboratory, Department of Hematology of Affiliated Taizhou Hospital, Wen Zhou Medical College, Linhai 317000, China. baoguochen@126.com
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Chen
authors.forename: Wei-Wu
authors.initials: WW
authors.lastname: Shi
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.forename: Wen-da
authors.initials: WD
authors.lastname: Luo
authors.forename: Qun-Yi
authors.initials: QY
authors.lastname: Guo
authors.forename: Bo-Li
authors.initials: BL
authors.lastname: Li
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors