Figure 1
Intravenous administration of cyclic STAT3 decoy suppressed xenograft tumor growth and downmodulated STAT3 target genes in the tumors of mice. (A) Mean tumor volume by day of treatment and treatment groups. UM-SCC1 cells (3 × 106 cells) were inoculated subcutaneously in the right flank of athymic nude mice. Mice were randomized after developing palpable tumors and were injected intravenously once a day, with 5 or 10 mg/kg of the cyclic STAT3 decoy or the mutant cyclic STAT3 decoy, or saline, for 2 wks (7 d/wk). Tumor volumes were measured three times a week using two-dimensional vernier calipers and measured to d 15. A significant decrease in tumor volume was observed in the mice treated with a cyclic STAT3 decoy (5 or 10 mg/kg) compared with the mutant cyclic STAT3 decoy group (p = 0.01) or saline (p = 0.01 for cyclic STAT3 decoy (5 mg/kg), p = 0.04 for cyclic STAT3 decoy (10 mg/kg)), as indicated by a nonparametric, two-tailed Mann-Whitney test. (B, C) At the end of the treatment period, the xenograft tumors were harvested and analyzed for STAT3 target gene expression, by performing immunoblotting for cyclin D1 and Bcl-XL. β-Tubulin was used to assess protein loading. In (B), the bar graph is a quantitative representation of cyclin D1/β-tubulin (p < 0.0001, p = 0.0078) and Bcl-XL/β-tubulin (p = 0.001, p = 0.024) in tumors from mice treated with cyclic STAT3 decoy (10 mg/kg) versus the saline or cyclic mutant control decoy (10 mg/kg), respectively. ln (C), the bar graph is a quantitative representation of cyclin D1/β-tubulin (p = 0.0004, p = 0.02) and Bcl-XL/β-tubulin (p = 0.0003, p = 0.0002) in tumors from mice treated with cyclic STAT3 decoy (5 mg/kg) versus the saline or cyclic mutant control decoy (5 mg/kg), respectively.