HMG-CoA reductase inhibitor simvastatin overcomes CAM-DR. (A) Integrin modulator and HMG-CoA reductase inhibitor simvastatin can overcome CAM-DR. NCI-H929 myeloma cells were treated for 48 hours with 20 μM melphalan in the absence or presence (suspension versus HS-5) of HS-5 stromal cells and PI uptake into CD38⁺ cells was determined by flow cytometry. Simvastatin (10 μM) was added as indicated in the figure. (B) Lovastatin overcame CAM-DR. Experiments were repeated with 1 μM lovastatin as described in panel A. (C) CAM-DR reversal is not mediated by de-adhesion. NCI-H929 (NCI) myeloma cells were incubated in the presence (+HS-5) or absence (in suspension) of HS-5 stromal cells and 10 μM simvastatin was added for 48 hours. The number of viable cells in suspension was determined by the WST-1 viability assay. (D) CAM-DR reversal is not mediated by reduced IL-6 secretion. NCI-H929 and HS-5 were coincubated as indicated and 10 μM simvastatin was added. IL-6 concentration in the supernatant was determined by ELISA. Mean values with standard deviations and P values are shown. n.s. indicates not significant.