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. 2018 Mar 7;6(1):17–32. doi: 10.1016/j.jcmgh.2018.02.013

Figure 4.

Figure 4

Selective uptake of targeted gastrin siRNA polyplex decreases orthotopic pancreatic tumor growth in vivo. (A) Final BxPC-3 tumor weights tended to be smaller in mice treated with 240 nmol/L siRNA, but this was not statistically significant. (B) Mice bearing human PANC-1 tumors and treated with 480 nmol/L targeted siRNA had significantly smaller tumors compared with controls. (C) Targeted siRNA are taken up into BxPC-3 orthotopic pancreatic tumors in mice. Polyplex that were either targeted to the CCK-B receptor or untargeted were loaded with fluorescently labeled Cy3 gastrin siRNA and injected intraperitoneally and imaged by fluorescent microscopy. Only the mice receiving the targeted siRNA showed fluorescent uptake within the tumors after 5 hours (arrows showing fluorescence). There was no uptake of fluorescent particles detected in the mice treated with untargeted polyplex circles show area of tumor and magnified view. (D) qRT-PCR for gastrin mRNA. Treatment with targeted siRNA had significantly less gastrin mRNA in PANC-1 tumors. (E1-5) Immunohistochemistry for gastrin peptide is shown from a representative BxPC-3 tumor from each treatment group. (E6) Densitometry analysis of immunostaining for gastrin reactivity showed significantly less gastrin (P = .02) in the tumors of mice treated with targeted siRNA. (F) Ki67 staining proliferation index was markedly reduced in PANC-1 tumors of mice treated with targeted siRNA (F1). PBS control Ki67 immunoreactivity (F2). Tumors treated with targeted NP with gastrin siRNA have reduced Ki67 immunoreactivity (F3). ∗P < .05, ∗∗∗P < .005.