Fig. 7

BKM120/HCQ combination treatment inhibited tumor growth in zebrafish and nude mouse xenograft models. A SKOV-3 and MKN-1 cells were labeled with Dil (red fluorescence) and injected into each embryo. The injected embryos were transferred to a 24-well plate containing 20 μM HCQ and/or 2 μM BKM120 and incubated for 72 h. The embryos were imaged with a fluorescence microscope to detect tumor growth and the resulting data were quantified, n = 8 in each group. Scale bar, 50 μm. B Representative images of the tumors from each group of nude mice upon treatment with vehicle, BKM120 (20 mg/kg/day), HCQ (30 mg/kg/day), or both drugs for the respective time periods. C Relative tumor volume at various time points of each group of nude mice (normalized to day 0). D Measurement of tumor weight after treatment for the respective time periods. E Time-course measurements of mouse weights every 3 days. F Representative images of H&E and TUNEL staining, and immunohistochemical staining analyses of Ki-67, p-ATM, BRCA1, BRCA2, Rad51, γH2AX and cleaved Caspase-3 in tumor tissues. Apoptotic cells in tumor tissues were detected by TUNEL staining. G Statistical quantification of (F). Scale bars, 50 μm. Graphs are normalized to the untreated group and shown as the mean ± SD from three independent experiments; **p < 0.01; ***p < 0.001