CCX721 does not reduce myeloma tumor burden through direct killing of myeloma cells. (A) MTT cellular proliferation assay of 5TGM1-GFP cells after overnight growth in the presence of increasing concentrations of CCX721 or the proteasome inhibitor bortezomib (n = 8 replicates per point, assay repeated n = 3 times). (B) Table of MTT cellular proliferation assay results (absorbance, mean ± SD) with cultured human myeloma cells grown for 3 days in the presence of CCX721 (1000nM) or bortezomib (10nM; n = 8 replicates per point, assay repeated n = 3 times). CCX721 data were not significantly different (P > .05) from control, but bortezomib data were (P < .05). (C) Plasmacytoma volume measured 21 days after 107 5TGM1-GFP cells were inoculated subcutaneously in naive C57BL/kaLwRijHsd mice. These mice were randomly assigned to receive vehicle (sesame oil) or CCX721 (100 mg/kg) twice daily by oral gavage for 21 days. Plasma levels of CCX721 were consistent with previous studies. ns indicates not significant. (D) Table of spleen weights (normalized to body weight) for the 2 dosing regimens; data were not significantly different from control (P > .05).
