Figure 5.

Cell-cycle decoy by telomerase-dependent adenovirus OBP-301 prevents chemotherapy-induced angiogenesis. FUCCI-expressing MKN45 cells (5×10⁶ cells/mouse) were injected subcutaneously into the left flanks of nestin-GFP transgenic nude mice. When the tumors reached approximately 6 mm in diameter (tumor volume, 80–100 mm³), mice were intratumorally injected with OBP-301 for 3 cycles every 3 d. (A, B) Representative images of cross-section of FUCCI-expressing MKN45 subcutaneous tumor treated with OBP-301 in nude mice (A) or nestin-GFP transgenic mice (B). (C) Histograms show cell-cycle phase of FUCCI-expressing MKN45 subcutaneous tumors treated with OBP-301. (D) Bar graphs show the number of tumor vessels in the surface area or the center area in tumor of control or treated with OBP-301 7 d after last treatment. (E) Bar graphs show the distance of tumor vessels from the surface area in control tumor or tumors, treated with OBP-301 21 d after last treatment. Data are shown as means ± SD (n = 5). Scale bars, 500 μm. G₀G₁-phase cancer cells are red; S-phase cancer cells appear yellow; and S/G₂-phase cells appear green in A, B, and represented as such in the histograms of C.