Figure 6

Inhibition of gemcitabine induced ISR pathway decreases PANC-1 orthotopic tumor growth. (a) PCCs were injected into the pancreas of athymic mice as described in Materials and Methods. High-resolution ultrasound images were obtained at 2 weeks post-PCC injection, and at indicated treatment times. Tumors are outlined and are representative images from six mice per group. (b) Tumor volumes were calculated using 3-D abdominal imaging. There was a step-wise decrease in tumor volumes from Vehicle-treated, to ISRIB-treated, to Gem-treated, and to Gem+ISRIB-treated mice. Data are the means±S.D.; ***P<0.05 compared with control, ^##P<0.05 compared with ISRIB. (c) H&E and PARP staining was performed on paraffin-embedded tissue sections (0.5 μm thick), bars=50 μm. (d) PARP-positive cells were counted and tabulated after normalization to percent of control. Data are the means±S.D. for four experiments. ***P<0.001, ^##P<0.001, ^$P<0.001 compared with control, ISRIB, and Gem+ISRIB treatments, respectively