The Effect Of CXCL12/CXCR4 Signal Axis On The Proliferation And Apoptosis Of Leukemic Cells Cultured With Human Umbilical Cord Blood-derived Mesenchymal Stem Cells

Objective: To investigate the role of CXCL12/CXCR4 signal axis and the effects of G-CSF and AMD3100 on the leukemic cells and their microenvironment in the co-culture model of HUCMSCs with HL-60(acute myeloid leukemia cell line)cells or Jurkat(acute lymphoblastic leukemia cell line)cells.Methods: HL-60 cells and Jurkat cells were co-cultured with human umbilical cord blood mesenchymal stem cells(HUCMSCs),and the model was managed with G-CSF,AMD3100 and their combination respectively.Cell viability and cell cycle were measured by Cell Counting Kit-8(CCK-8).Cell apoptosis was assessed by flow cytometry using the Annexin V Apoptosis Kit,as well as the cell-cycle analysis.The expression of surface CXCR4 protein and total CXCR4 protein of leukemic cells were detected by flow cytometry and Western blot respectively.Results: HUCMSCs could decrease the viability of HL-60 cells and Jurkat cells and the percentage of apoptotic cells,they can also increase the number of quiescent cells,while G-CSF and AMD3100 could further reduce the proliferation of HL-60 cells and Jurkat cells in HUCMSC co-culture model,destructed the anti-apoptotic effect of HUCMSC on HL-60 cells and Jurkat cells,and the combination of two drugs resulted in a synergistic effect.G-CSF could reduce the expression of surface CXCR4 protein and total CXCR4 protein in leukemic cells,while AMD3100 could only decrease the expression of CXCR4 on the surface of leukemia membrane,having no effect on the expression of CXCR4 protein in cytoplasm.Conclusion: Human umbilical cord blood mesenchymal stem cells can inhibit the proliferation and apoptosis of acute leukemia cells and increase the number of G0 / G1 phase cells in leukemic cells.AMD3100 can decrease the expression of surface CXCR4 protein in leukemia cells,G-CSF can decrease total CXCR4 protein as well as membrane CXCR4 protein expression.Both of them can block the CXCL12/CXCR4 signal axis,weakening the relationship between leukemia cells and microenvironment.And on the basic of HUCMSC influenced leukemia cells' growth and proliferation,AMD3100 and G-CSF can weaken their cell viability and promote its apoptosis,and decrease the percentage of G0 / G1 phase cells in leukemia cells.