Figure 5
AdLCY had higher oncolytic activity than Ad9OC against TCC-SUP xenografts and syngeneic MBT-2 tumors. (a, b) Groups of NOD/SCID mice (n=5-6) were subcutaneously inoculated with TCC-SUP cells (5 × 106) on day 0, and intratumorally treated with 5 × 108 PFU of AdLCY or Ad9OC, or with saline on days 21, 23 and 25. Tumor volumes (a) and Kaplan–Meier survival curves (b) were determined. (c, d) Groups of C3H/HeN mice (n=8) were subcutaneously inoculated with MBT-2 cells (5 × 106) on day 0, and intratumorally treated with 5 × 108 PFU of AdLCY or Ad9OC, or with saline on days 11, 13 and 15. Tumor volumes (c) and Kaplan–Meier survival curves (d) were determined. Values are the mean±s.e.m. of the mean. ***P<0.001; **P<0.01; *P<0.05. (e) NOD/SCID mice were inoculated with TCC-SUP cells and then treated with AdLCY, Ad9OC or AdLacZ as described in a, tumors were excised on day 31, and serial formalin-fixed paraffin sections of tumor tissues were immunohistochemically stained for adenovirus type 5 (Ad5) proteins, HIF-1α, CD44 and CD133. Representative images in each group are shown (scale bar=50 μm). Images shown at × 400 magnification correspond to the boxed areas in the images shown at × 200 magnification. Colocalization of Ad5 with CD44 and with CD133 is indicated by arrows and arrowheads, respectively. Background staining was determined by substituting isotype control IgG for the primary antibody.
