Figure 5.

Pancreatic stellate cells do not prevent the anti-tumorigenic action of SG3299. A, Athymic CD1Nu/Nu female mice bearing human Panc0403+PS1 xenograft tumours were treated with NT-peptide (black square), SG3511 (red filled triangle) or SG3299 (blue unfilled triangle) (20 μg/kg; i.p administration) bi-weekly for 4 consecutive weeks (start of treatment day 0). Data are presented as mean tumor volume (error bars represent SEM, n=4 mice/group). Treatment commenced when tumors reached 100 mm³. B, Micrographs of Panc0403+PS1 tumor xenografts from mice treated as in (A) (n=4/treatment, after 4 weeks treatment). Tumors were harvested, fixed, paraffin-embedded and sections subject to immunohistochemical staining for the indicated molecules of interest including pan-cytokeratin (CK, epithelial marker), Ki67 (proliferation), αvβ6, cleaved-caspase 3 (Cl.Caspase 3; apoptosis), E-cadherin (epithelial marker), blood vasculature (endomucin), activated fibroblasts (α-sma), vimentin (stroma) and γH2AX (DNA damage/adduct formation). Representative images are shown of the 4 tumors harvested for each treatment. Magnification bar=2000 μM for x1 magnification images, magnified images (x50) are of indicated region of interest (tumor cells), with a scale bar of 50μM. C, Bar graph of composition of xenografts (% CK+ cells=white bar, % necrotic area in gray and % stroma is in blue) from (A) and histograms of marker expression shown in (B). Staining assessed & scored by 2 individuals or using VisioPharm computational analysis software (n=4 individual tumors, error bars represent SEM). *P=0.05, **P=0.01, ***P<0.001 (relative to PBS or indicated treatment).