Amlodipine extends survival in orthotopic xenografts of GR tumor cells. (A–C) PANC-1-GR cells were transduced with stable expression of firefly luciferase (PANC-1-GRLuc), and 0.8 × 106 cells were implanted into the pancreas of NSG mice. Disease progression was monitored by IVIS, and once animals developed 100-mm3 tumors, they were enrolled into one of four treatment groups. Mice were given IP injections of a PBS vehicle (n = 5), 100 mg/kg gemcitabine twice per week (n = 7), 2 mg/kg amlodipine daily (n = 5), or twice weekly gemcitabine with daily injections of amlodipine (n = 9). Mice were killed when showing clear signs of health decline such as weight loss or lethargy, and survival is shown via the Kaplan–Meier method. (D) At the study end point, gross changes in the pancreas, liver, and spleen were evaluated and representative images are shown for each group. (E) Tissues also were stained with H&E, and representative images are shown for tumors in the pancreas and liver. Arrows point to areas of tumor tissues. (F) The percentage of mice in each group showing metastatic lesions to the liver, spleen, and/or body wall. (G and H) Tissues were stained with H&E or via immunohistochemistry for pERK or PCNA and quantified as described, and results are displayed as individual value plots.