Figure 3
HIF-1-mediated metabolic reprogramming during the metastatic colonization of cancers in the lungs.
(a) Athymic nude mice were i.v. transplanted with a suspension of the stable transfectant, EMT6/CMVp-Cluc/5HREp-Luc (1 × 106/mouse). Tumor-bearing mice were treated with saline (-), NAC (1,000 mg/kg/administration, 2 injections/day from days 1 to 6), or YC-1 (30 mg/kg daily from days 3 to 6). On the indicated days after the i.v. transplantation, LDHA (green) and p-PDH-E1α (red) were detected in the lungs with the resultant metastatic tumors (dotted line). Hoechst33342 = counter staining (blue). Bar = 50 μm. (b–d) Athymic nude mice were i.v. transplanted with a suspension of EMT6/CMVp-CLuc/5HREp-FLuc cells and treated with or without the HIF-1 inhibitor, YC-1 (30 mg/kg daily) from 3 to 6 days after the transplantation of cancer cells. Six days after the transplantation, mice were subjected to the in vivo CLuc assay for tumor volume (b) and to the optical in vivo imaging experiment for HIF-1 activity (c). HIF-1 activity in lung metastases was divided by CLuc activity in the serum to calculate HIF-1 activity per unit of metastatic lung tumors (d). Means ± s.d. n = 10. *P < 0.05. **P < 0.01. NS = not significant.
