title: [Effects of SDF-1/CXCR4 signal pathway blockade by AMD3100 on the adhesion of leukemia cells to osteoblast niche and the drug resistance of leukemia cells].
abstract: OBJECTIVE
  To study the blocking effect of CXCR4 inhibitor AMD3100 on the adhesion of leukemia cells to osteoblast niche, and the reversal of multidrug resistance in leukemia cells.
  
  
  METHODS
  Mesenchymal stem cells (MSCs) from leukemia patients were planted on the bio-derived bone scaffolds and then induced into osteoblasts to establish the bio-osteoblast niche. The levels of SDF-1were tested with ELISA. The leukemia cell line MV4-11 cells with FLT3-ITD mutation were inoculated into the bio-osteoblast niche to build a three-dimensional co- culture system. The expression level of CXCR4, adhesion and apoptosis rates of leukemia cells were observed by flow cytometry after incubation with AMD3100 and Ara-C for 24 h and 48 h.
  
  
  RESULTS
  (1)The supernatant levels of SDF-1 in cultured osteoblast were (304 ± 18), (410 ± 28) and (396 ± 16) pg/ml on 7 th, 14 th and 21 th day, respectively. It reached the highest on 14 th day. The expression level of CXCR4 in cultured MV4-11 cells was (72 ± 16)%. (2)Adhesion rate of MV4-11 cells to osteoblast niche was (40.1 ± 8.1)% after AMD3100 treatment for 24 h, while that of control group was (65.6 ± 12.1)% (P<0.05). (3)The apoptosis rate of MV4-11 cells incubated with AMD3100 for 24 h was (5.6 ± 0.8)%, while that of control group was (2.5 ± 0.5)%. The apoptosis rates of AMD3100-induced MV4-11 cells were (10.0 ± 2.4)%, (17.8 ± 2.3)% and (25.1 ± 2.4)% after treatment with Ara-C at 0.02, 0.20, 2.00 mg/ml respectively and they were (6.7 ± 1.0)%, (10.3 ± 1.5)%, (16.2 ± 3.1)% respectively in AMD3100-noninduced control group, the difference was significant (P<0.05).
  
  
  CONCLUSIONS
  AMD3100 can block the interaction between osteoblasts niches and leukemia cells, and play an important role in the reversal of multidrug resistance in leukemia cells.
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Kong
mesh_terms: D017209:Apoptosis; D001596:Benzylamines; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12; D018920:Coculture Techniques; D000080027:Cyclams; D003561:Cytarabine; D004351:Drug Resistance; D005434:Flow Cytometry; D006571:Heterocyclic Compounds; D006801:Humans; D007938:Leukemia; D059630:Mesenchymal Stem Cells; D010006:Osteoblasts; D019718:Receptors, CXCR4; D015398:Signal Transduction
chemical_list: D001596:Benzylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D003561:Cytarabine; C088327:plerixafor