Extended Data Fig. 5: Glutaminase inhibitor CB-839 suppresses the growth of ARID1A-inactivated OCCCs in vivo.
a, Schematic of experimental design and reference time of the mouse experiment. Cells were orthotopically transplanted into non-obese diabetic/severe combined immunodeficiency gamma (NSG) mice and allowed to establish for one week. After the tumors presented palpable masses, the mice were randomized into various treatment groups and treated for an additional three weeks. At the end of treatment of three weeks, mice from various treatment groups were euthanized for measuring tumor weight as a surrogate for tumor burden or followed for survival experiment. b-c, Orthotopic xenografts formed by ARID1A knockout (b) or control RMG1 cells (c) were treated with vehicle or CB-839 for 3 weeks (n=7 mice/group). At the end of the treatment, tumor weight was measured as surrogate for tumor burden. d-e, Tumors dissected from b-c, were subjected to immunological staining for GLS1, cell proliferation marker Ki67, mitotic marker serine 10 phosphorylated histone H3 (pH3S10) or apoptosis marker cleaved caspase 3 on serial sections (d) and the histological score (H-score) of the indicated markers was quantified from three separate fields from seven tumors from seven individual mice in each of the indicated treatment groups (e). Scale bar = 100 μm. f, Orthotopic xenografts formed by ARID1A-mutated TOV21G cells were treated with vehicle or CB-839 for three weeks (n=6 mice/group). Body weight of tumor bearing mice was measured at the indicated time point. Error bars represent mean with s.d. in b, c, e and f. P values were calculated using two-tailed Student t-test in b, c and e.
