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. 2013 Jul 18;4(7):e728. doi: 10.1038/cddis.2013.259

Figure 6.

Figure 6

The combination of Reolysin and BZ strongly reduces tumor burden in the Panc-1 xenograft model. (a) Panc-1 cells (1 × 107 per mouse) were injected into the flanks of nude mice. When tumors reached approximately 150 mm3 in size, mice were randomized into groups and treated with 0.5 mg BZ per kg Q3D, 5 × 108 TCID50 Reolysin Q7D, or both agents for 5 weeks. Tumors were measured twice weekly. Mean±S.E.M., n=8. *Indicates a significant difference compared with vehicle, or **indicates a significant difference compared with either single-agent treatment. P<0.05. Reolysin and BZ are well tolerated in vivo. Animal body weight was determined at the end of the study (day 38) to quantify drug-induced weight loss. Mean±S.D., n=8. (b) Reovirus replicates in tumors in vivo. Electron microscopy was performed on tumors collected from Reolysin-treated animals and revealed the presence of reovirus. Images shown were taken from an animal treated with the Reolysin+BZ combination. Arrows denote the presence of reovirus. Similar results were observed in mice treated with Reolysin alone. (c) Reolysin and BZ increase BiP expression. BiP expression was measured by IHC, and staining intensity was quantified using ImageJ software. *Indicates a significant difference compared with controls, and **denotes a significant difference compared with either single-agent treatment group (P<0.05). (d) Apoptosis was measured by TUNEL staining. Quantification was conducted by manually counting TUNEL-positive cells. Mean±S.D., n=5. *Indicates a significant difference compared with controls, and **represents a significant difference compared with single-agent treatments P<0.05