Figure 2

Suppression of integrated stress pathway enhances gemcitabine chemosensitivity. (a) AsPC-1 cells were incubated with ISRIB alone or (b) Gem alone, or ISRIB and Gem for 72 h as indicated, and MTT assays were performed. Data are the means±S.D. from three experiments. *P<0.001 compared with control, **P<0.005 compared with Gem alone, #P<0.005 compared with Gem (1 μM)+ISRIB (250 nM). (c) PANC-1 cells were incubated with ISRIB alone or (d) with Gem alone or with Gem+ISRIB for 72 h as indicated, and MTT assays were performed. Data are the means±S.D. from three experiments. *P<0.001 compared with control, **P<0.005 compared with Gem alone, $P<0.005 compared with 0.1 μM Gem+250 nM ISRIB. (e and g) AsPC-1 cells were incubated with 0.5 μM ISRIB alone or in combination with 10 μM Gem. (f and h) PANC-1 cells were incubated with 0.5 μM ISRIB alone or in combination with 1 μM Gem. Cell lysates were immunoblotted for cleaved caspase-3 protein in (e and f) and caspase-3/7 activity was measured in (g and h). Data shown are from three independent experiments in (e and f). Data are the means±S.D. from three experiments in ( g and h). ##P<0.01 compared with control and ISRIB, ***P<0.01 compared with control, ISRIB, and Gem