Fig. 2

Inhibition of GLS with CB-839 or depletion of cellular glutamine in combination with metformin reduces OS cell growth. a–d The proliferation responses of OS cells to the treatments of CB-839 and metformin alone or in combination. OS cells of human MG63.3 (a), 143B (b), and murine K7M2 (c) were treated with vehicle, CB-839 (1 μM), metformin (1 mM for MG63.3 and 5 mM for 143B and K7M2) as a single agent or in combination for 3–7 days until the vehicle-treated cells reached 100% confluency. d Phase-contrast images of CB-839 and metformin treated MG63.3 cells. e Synergy combination index data. f The proliferation responses of MG63.3 cells to the deprivation of glutamine (0.5 mM) or in the combination with metformin (1 mM). Statistic analysis is used ANOVA followed by multiple comparisons “vehicle vs each treatment,” *p < 0.05, **p < 0.01, ***p < 0.001