Fig. 1

Restricted ketogenic diet with DON reduces progression and mortality of the VM-M3 GBM. VM/Dk inbred mice were implanted orthotopically with a small (1.0 mm × 1.0 mm) tissue fragment from the VM-M3 tumour on day 0. The implanted mice were divided into two groups on day 4 and were fed either a standard chow diet unrestricted or ad libitum (SD-UR), or a ketogenic diet (KD-R) in restricted amounts to reduce body weight by about 15%. DON (0.1–1.0 mg/kg) was injected i.p. 7 days following orthotopic tumour implantation. The diet feeding was continued and DON was injected every day or every alternate day as shown in (a). All mice were imaged in vivo and terminated on day 14 or 15 when all control mice appeared moribund (experiments 1, 2). For experiment 1, bioluminescence was scored from 0–4, following the administration of lower doses of DON (0.1 and 0.5 mg/kg). Values are expressed as the mean ± SEM and a one-way analysis of variance followed by Tukey’s post hoc test was performed to determine the significance between groups (b). In experiment 2, in vivo bioluminescent photon values were obtained following the administration of DON (1.0 mg/kg) in mice under the KD-R (c). The average in vivo bioluminescent photon values were calculated for the KD-R (n = 4 mice) and KD-R + DON (n = 8 mice) in experiment 2. Values are presented as the mean ± SEM and the P value was calculated using a two-tailed student’s t-test (d). In vivo bioluminescent images of three representative mice from both study groups in experiment 2 are shown in (e). For experiment 3, a survival study was performed and a Kaplan–Meier survival plot was configured for SD-UR (n = 15 mice), SD-UR + DON (n = 10 mice), KD-R (n = 10 mice), and KD-R + DON (n = 10 mice) (f). The log-rank statistical analysis test showed a significant difference between groups in this survival study. Source data are provided as  Supplementary Data 1