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 / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSION</b>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.</p>