Fig. 7

Pharmacological inhibitors of Lsd1 inhibit growth of Gfi1-driven MB. a, b In vitro proliferation assays for MG and MP tumor cells treated with a GSK-LSD1 or b ORY-1001. Proliferation was measured via ³H-thymidine incorporation at 48hrs. c Cell viability of post-mitotic granule neurons treated with GSK-LSD1 (blue) or ORY-1001 (purple). Viability was measured via CellTiter-Glo Luminescent Assay at 48 h. Data shown in a–c are from representative experiments and are plotted as the means of technical triplicate samples ± SEM. All experiments were repeated in at least three biological replicates. d–h Mice implanted with subcutaneous MG tumors underwent surgical resection of tumors and were subsequently treated with vehicle (saline) or 10 mg/kg GSK-LSD1 in cycles of four days on and three days off (vehicle n = 21, GSK-LSD1 n = 22). d Representative images of two tumors before (left) and after (right) surgical resection. Tumors are outlined by white dotted lines. Tumor growth was monitored weekly by e bioluminescent imaging and f caliper measurements. Red arrowhead indicates time of surgical resection. Blue arrowhead indicates start of drug treatment. Data shown are from a representative experiment and are plotted as the means ± SEM. When tumors reached the maximum allowed diameter, mice were sacrificed and resulting tumors were g collected and h weighed. Compared to resection alone, resection and GSK-LSD1 treatment significantly reduced tumor burden in mice. p < 0.0001, t = 6.042, df = 41, one-tailed unpaired t test. Data shown in h are from three replicate experiments and plotted as the means ± SD