AMD3100 overcomes drug resistance to induction of apoptosis by therapeutic agents in MM cell lines induced by BMSCs in vitro. Apoptosis assay measured using Annexin staining by flow cytometry. (A) AMD3100 did not enhance the effect of bortezomib (2.5-5 nM) for 24 hours on MM.1S cells when those were cultured without BMSCs. However, treatment with AMD3100 (50 μM) restored the sensitivity to bortezomib which was reduced as a result of coculture with BMSCs in the MM cell lines MM.1S (B), RPMI 8226 (C), and OPM-2 (D). Cells were treated with bortezomib either alone or in the presence of AMD3100 (50 μM). This effect was not unique to bortezomib, but AMD3100 was shown to increase the sensitivity of MM.1S cells to treatment with dexamethasone 25 nM, melphalan 10 μM, and doxorubicin 150 nM for 24 hours (E). *P = .003; **P < .001; ***P = .010; #P = .027; ##P = .048. Error bars represent SD.