Fig. 5

GLS1 inhibition sensitizes pancreatic cancer to ß-lap in vivo. a Clonogenic survival of MiaPaCa2 and ASPC1 cells pre-treated with 1 μM CB-839 for 48 h followed by 2 h of ß-lap dose response. b Subcutaneous tumors grown from MiaPaCa2 cells in nude mice were allowed to reach a volume of 100 mm³, after which, the mice were treated every other day with vehicle (HPßCD, n = 6), sub-efficacious dose of CB-839 (oral gavage, 200 mg/kg, twice daily for 10 days, n = 8), sub-efficacious dose of ß-lap (IV, 25 mg/kg, n = 8) or sub-efficacious doses of CB-839 and ß-lap (n = 10) for a total of five doses (arrows). Tumor growth was monitored until tumors reached 1000 mm³. Error bars, SEM. c Survival of tumor-bearing mice represented as a Kaplan–Meier plot. The mice were sacrificed when tumors reached 1000 mm³. Statistically analyzed with the log-rank test for trend. d Western blot of PAR and γH2AX from a set of tumors harvested 30 min after treatment with ß-lap ± CB-839 (4-day treatment), n = 3 tumors per group, same doses as above. e Relative GSH/GSSG ratio in treated groups normalized to microgram of tumor protein. Unless stated otherwise, all results were compared using Student’s t tests. *p < 0.05; **p < 0.01; ***p < 0.001