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Fig. 5 | Journal of Translational Medicine

Fig. 5

From: Platinum-induced mitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer

Fig. 5

OXPHOS inhibition blocks the platinum-induced enrichment of ALDH + cells in vivo. A 2 × 106 OVCAR3 cells were injected s.c in 6–7 weeks old NSG mice. Once the tumors were  > 100 mm3, mice were randomized into three groups and treated with vehicle alone or combination of vehicle + carboplatin or IACS-010759 for 3 weeks as indicated. At the end of the study, tumors were collected, dissociated into single cells and the ALDEFLUOR assay was performed. B Tumor volumes were measured using a digital caliper through 3 weeks of treatment by the same investigator throughout the study. N = 4–5 mice per group. *P relative to carboplatin + vehicle. #P relative to vehicle. C Percentage of ALDH + cells in dissociated xenograft tumor samples using ALDEFLUOR assay. D Expression of glycolysis and OXPHOS genes in tumor xenografts. Graph indicates mean ± SEM in the different treatment groups. N = 4–5 mice per group. For all treated with vehicle alone versus carboplatin + vehicle or IACS-010759, P values *< 0.05, **< 0.005, ***< 0.0005, ****< 0.0001. E Western blot of the indicated proteins in whole cell lysates from tumor xenografts. F Model for how platinum treatment of HGSOC cells results in increased mitochondrial activity that contributes to the platinum-induced enrichment of ALDH + OCSCs. Platinum induces an increase in SIRT1 activity that increases TFAM levels, which in turn likely increases expression of OXPHOS genes that leads to an increase in mitochondrial activity

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