The image contains multiple graphs and a western blot analysis. Panel A shows a line graph depicting the body weight of nude mice bearing H C T 116 tumors over five treatment days. The graph compares vehicle treatment with two doses of H I F i administered orally twice daily (O G, B I D). Panel B presents a line graph of tumor volume over the same period, showing a significant reduction in tumor growth with H I F i treatment compared to vehicle. Panel C displays a western blot analysis of H I F-1 alpha and beta-actin expression in tumor lysates collected at different time points post-treatment. Panel D features a line graph showing plasma concentration of H I F i over time following intraperitoneal (I P) or oral gavage (O G) administration. Panel E includes a bar graph illustrating relative m R N A expression levels of C a 9 and A d m in C T 26 cells treated with vehicle, 1.21 S 9 N, or P T 2385 under different oxygen conditions. Panels F through J show individual tumor growth curves for C T 26 tumors treated with various compounds. Each graph includes mean values with standard deviations, and significant differences are indicated with asterisks. All data is approximate.
Analysis of mice treated with 1.21S9N or 3.2.16. Related to Fig. 8. (A and B) Nude mice bearing HCT116 tumors were administered vehicle or HIFi (80 mg/kg OG BID). BW (A) and tumor volume (B) were measured. Data are presented as the mean ± SD, n = 5. ***P < 0.001 versus vehicle by two-way ANOVA with Dunnett’s multiple comparisons. (C) Lysates were prepared from tumors collected 8, 16, or 24 h after the last dose of HIFi or vehicle and probed for HIF-1α and β-actin expression by immunoblot assay. (D) Plasma concentration of HIFi (mean ± SD, n = 1-3 mice each) was measured at the indicated time (hours) following IP or OG administration of a single dose. (E) CT26 cells were incubated for 24 h at 20% O2 with vehicle or at 1% O2 with vehicle, 1.21S9N, or PT2385. RNA was isolated and analyzed by RT-qPCR using primers specific for Ca9 and Adm. Data are presented as the mean ± SD (n = 3). ****P < 0.0001 versus vehicle–1% O2, by two-way ANOVA with Dunnett’s multiple comparisons. (F–J) Individual CT26 tumor growth curves are shown for data presented in Fig. 9 A. Source data are available for this figure: SourceData FS5.