Effect on tumor growth of mixed backbone VEGF antisense oligonucleotides in vivo.

Tumor xenografts were initiated by subcutaneous inoculation of cell lines in the lower back of BALB/C nu/nu athymic mice as described in “Materials and methods.” AS-3m was administered intraperitoneally daily for the study duration. (A) Effect of AS-3m on ovarian (Hey) tumors. Tumor growth curve in BALB/C athymic mice, which lack mature T-cells (left panel), and SCID beige mice in which T cells and B cells are absent and NK cells and macrophages are nonfunctional. In the absence of any appreciable immune function, AS-3m has antitumor activity. (B) Effect of combined treatment with AS-3m and chemotherapy (Taxol) on 5-day established M21 tumor xenografts. AS-3m or PBS was injected intraperitoneally daily beginning day 5. Taxol (2.5 mg/kg) was given intraperitoneally on days 5 and 12. The left panel shows dose response to AS-3m alone. The right panel shows results of combined treatments. Final tumor weights are shown to the right of the growth curves in each graph. Data represent the mean ± SD of 6 mice in each group.