AMD3100阻断SDF-1 /CXCR4信号通路对白血病细胞与成骨龛黏附及耐药性的影响

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: ①The supernatant levels of SDF-1 in cultured osteoblast were (304±18), (410±28) and (396±16) pg/ml on 7th, 14th and 21th day, respectively. It reached the highest on 14th day. The expression level of CXCR4 in cultured MV4-11 cells was (72±16)%. ②Adhesion rate of MV4-11 cells to osteoblast niche was (40.1±8.1)% after AMD3100 treatment for 24h, while that of control group was (65.6±12.1)% (P<0.05). ③The apoptosis rate of MV4-11 cells incubated with AMD3100 for 24h 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, 2.00mg/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). CONCLUSION: 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.