Fig. 7: Disulfiram (DSF) inhibits tumor-growth and targets tumor-promoting macrophages.
a Effect of DSF on B16 and LLC tumor metastasis in C57BL/6 mice (n = 7 for B16 and n = 5 for LLC). b Effect of oral DSF (from 4 days after tumor inoculation) on LLC subcutaneous tumor growth (n = 10). c Numbers of Ly-6Chi and Ly-6Clo monocytes/macrophages and neutrophils in tumors, and proportion of CD206+ M2-type cells among tumor-associated macrophages (CD45+CD11b+CD24−Ly-6G− cells in leukocyte gate) on day 20 after tumor inoculation. (n = 5). d Accumulation of macrophages (F4/80, red) around metastatic lung nodules (broken outline) (day 12 after B16 tumor cell injection). Three visual fields were averaged. e Effect of DSF on tumor growth in the MMTV-PyVT spontaneous mammary tumor model. Representative image of tumor at treatment start (day0) (left), individual tumor sizes at day0 and 39 (middle) and combined growth rate curves of each tumor (4 mice each group, 10 mammary tumor sites per mice). f Effects of 48-h in vitro culture in the presence of DSF, the cytotoxic anti-cancer drug 5FU, and the NF-κB inhibitor IKK-IV on LLC tumor cell growth (left panel, WST-1 assay, s.e.m. for the control = 1.298) and toxicity (right panel, LDH cytotoxicity assay) (assayed in triplicate, representative of three independent experiments, s.e.m. for the control = 0.5201). g Direct action of DSF on monocyte-derived macrophages function to influences tumor cell growth in vitro. The experiment was repeated three times. *P < 0.05, **P < 0.01, ****P < 0.0001 by two-tailed unpaired Student’s t-test. Error bars indicate s.e.m. Scale bars, 50 μm.
