Figure 9.

Depletion of CAPaSC by ProAgio decreases metastasis and poorly differentiated tumors. (A) Representative images of H&E staining of liver tissue sections of GEM-KPC mice treated with the indicated agents. Liver metastasis lesions were confirmed under the microscope and marked by a black dotted circle in the images. (B and C) Percentage of GEM-KPC mice treated with vehicle or 10 mg/kg ProAgio that show a different number of liver metastatic nodules (>5, >5 nodules; 1–5, 1–5 nodules; 0, no metastatic nodule) (B); and the number of metastatic nodules in the liver of GEM-KPC mice treated with vehicle or ProAgio (C). Metastatic nodules were assessed by gross inspection of the liver of each treated mouse by naked eye or under the microscope. (D and E) Representative images of IHC staining of Hif-1α (D), and quantitative analyses of Hif-1α stain (E, Hif-1α⁺ area [fold], fold change by comparison with the mean value of the ProAgio group as 1) in tumor sections of GEM-KPC mice treated with vehicle or ProAgio. (F and G) In vitro scratch wound healing assay of KPC 961 cells cultured under hypoxia and untreated (left) or treated with IGF1 (right) compared with those cultured under normoxia as a control (F) and quantitative analyses of the migrating cells in the scratched areas (G). (H and I) The scratch wound healing assay of KPC 961 cells cultured under hypoxia and treated with the indicated concentrations of IGF1 for the indicated amounts of time, compared with those cultured under normoxia as a control (H) and quantitative analyses of the migrating cells in the scratched areas after IGF1 treatment (I). (G and I) Error bars represent means ± SEM. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001. Hif, hypoxia-inducible factor; n.s., denotes not significant.