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Extended Data Fig. 10 | MCT1 inhibition reduces the levels of PPP, but not
glycolytic, metabolites. Related to Figs. 3 – 5. a, The GSH to GSSG ratios in
melanoma cells from mice treated with AZD3965 or DMSO (two independent
experiments per melanoma). b, Quantitative analysis of NADPH and NADP+ in
melanoma cells from mice treated with AZD3965 or DMSO (one or two
experiments per melanoma). Liver cells were included as a control, with a high
NADPH/NADP+ ratio. c, Expected isotope-labelled species after infusion of
[1,2-^13 C]glucose. d, Glucose m + 2 as a fraction of total plasma glucose in mice
xenografted with efficiently metastasizing melanomas (M405, M481 and
UT10), treated with DMSO or AZD3965 and infused with [1,2-^13 C]glucose.
e, Glucose m + 6 as a fraction of total plasma glucose in mice infused with [U-^13 C]
glucose. The number of mice per treatment is indicated (two independent
experiments). f–i, LC–MS measurement of the levels of glycolytic (f, h) and
oxidative PPP (g, i) metabolites in subcutaneous tumour cells from mice
xenografted with melanomas treated with DMSO (control) or AZD3965 (MCT1
inhibitor) for 7 days. j, Flow cytometrically isolated MCT1high or MCT1−/ low
melanoma cells were subcutaneously transplanted into NSG mice, using 10 or
100 cells per injection. All injections formed tumours. Rate of growth of the
tumours initiated with 10-cell injections. Data are mean ± s.d. Statistical
significance was assessed using t-tests (a), repeated-measures two-way
A N OVA s (b), t-test (e, 180 min), log 2 -transformed two-way ANOVAs (f, h),
log 2 -transformed t-tests (g, M405 and UT10), Mann–Whitney test (g, M481
and i, M481), Welch’s t-tests (i, M405 and UT10) or using nparLD test (d, j).