Fig. 3.

GRP78 small molecule inhibitors reduce KRAS protein level in vitro and in vivo. A427 (A), H460 (B), HCT116 (C), LS180 (D), PANC-1 (E), and CFPAC-1 (F) cells were treated with either DMSO, HA15 (10μM) or YUM70 (10μM) for 24 hr. The superscript indicates the KRAS mutation for each cell line. Whole cell lysate was subjected to Western blot analysis for KRAS protein level with GAPDH serving as loading control. The quantitation of the relative KRAS protein level after normalization to GADPH levels is shown in the graphs below. (G) Schematic illustration of the pancreatic cancer xenograft experiment and treatment conditions. (H) MIA PaCa-2 xenograft tumor tissues were harvested from the mice at the end of the treatment and subjected to Western blot analysis for KRAS protein level with GAPDH serving as loading control. The quantitation of the relative KRAS protein level after normalization to the GAPDH levels is shown in the graph on the right. Data are presented as mean ± S.D. * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001, ns: not significant (Student's t test).