[Effects of anti-CXCR4 monoclonal antibody on adhesion and proliferation of human acute myelocytic leukemia cell line HL-60].
OBJECTIVE
Stromal cell derived factor-1 (SDF-1), excreted by bone marrow stromal cells, may be involved in shielding of marrow stromal cells from leukemia cells by binding to its receptor CXCR4, but the relation between SDF-1/CXCR4 axis and leukemia cells is unclear. This study was to inhibit activity of SDF-1 by anti-CXCR4 monoclonal antibody 12G5, observe changes of adhesion and proliferation of acute myelocytic leukemia cell line HL-60 co-cultivated with leukemic marrow stromal cells, and to assay potential of inhibiting SDF-1-driven processes on treating marrow residual disease.


METHODS
HL-60 cells were co-cultured with leukemic marrow stromal cells, and 10 mug/ml 12G5 was added to block SDF-1 activity. Adhesive state, adhesion rate, apoptosis rate, and cell cycle of HL-60 cells were observed after incubation. Living conditions of HL-60 cells were detected by trypan blue exclusion, cell growth curve was protracted.


RESULTS
Adhesion rate of 24-h 12G5-incubated HL-60 cells was (39.4+/-7.9)%, while that of control HL-60 cells was (51.4+/-5.9)% (P< 0.05). G0/G1, S, and G2/M phases of 24-h 12G5-incubated HL-60 cells were (55.2+/-4.9)%, (30.4+/-4.1)%, and (14.4+/-5.2)%, respectively, and apoptosis rate was (9.0+/-1.7)%; while those of control HL-60 cells were (44.7+/-2.2)%, (45.3+/-3.7)%, (10.0+/-2.6)%, and (4.0+/-2.4)%, respectively. T test showed that 12G5 induced more cells entering G0/G1 phase (P< 0.05), and increased cell apoptosis rate(P< 0.05). Compared with control HL-60 cells, survival rate and proliferation of 48-h 12G5-incubated HL-60 cells decreased markedly.


CONCLUSIONS
12G5 may inhibit adhesion ability and proliferation of HL-60 cells, thus inhibiting SDF-1 activity by 12G5 may be helpful to the treatment of marrow residual disease.
Wei
Li
L
Department of Hematology, XinQiao Hospital, The Third Military Medical University, Chongqing 400 037, P.R. China.
Kong
Pei-Yan
PY
Chen
Xing-Hua
XH
Peng
Xian-Gui
XG
Zeng
Dong-Feng
DF
Chang
Cheng
C
Yang
Wen-Bo
WB
Liu
Hong
H
Liu
Lin
L
Wang
Qing-Yu
QY
Zhang
Yi
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002469:Cell Separation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D018920:Coculture Techniques; D018922:HL-60 Cells / Q000166:cytology; D006801:Humans; D019718:Receptors, CXCR4 / Q000276:immunology*; D017154:Stromal Cells / Q000473:pathology
D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4