GLUT4-specific glucose transport inhibition elicited by the HIV therapeutic ritonavir suppresses myeloma growth and viability. (A) KMS11 and (B) L363 cells were plated in 5mM glucose medium with ritonavir or DMSO (D) for 17 hours. Glucose consumption rates are normalized to untreated cells (not shown). (C) KMS11 and (D) L363 cells were treated with ritonavir or DMSO for 72 hours. Relative viable cell numbers were determined by MTS assay and normalized to untreated cells (not shown). (E) Stable KMS11 cell lines were generated expressing empty vector or GLUT1 and GLUT1 levels were assessed by immunoblot analysis. Representative blot is shown. N.S. indicates nonspecific band. (F) Stable cell lines from panel E were treated with DMSO or ritonavir (Rit) for 5 hours, and glucose consumption was assessed. (G) Cell proliferation was measured in the stable cell lines described in panel E treated with ritonavir (Rit) or DMSO for 72 hours. A representative experiment is shown. (H) Cell proliferation rates from multiple experiments represented by panel G are normalized to DMSO-treated cells. (I) Primary myeloma cells were treated with DMSO or ritonavir for 72 hours before annexin V/DAPI staining. Values are normalized to DMSO-treated samples (n = 1 for each patient sample). (J) Diagram highlights alterations in glucose transporter regulation between NBLs/plasma cells (top) and MM cells (bottom). (A-D,F,H) Data are mean ± SEM. (A-H) n ≥ 3. *P < .05. **P < .01. ***P < .005.