Figure 6
Figure 6. Hsp90 inhibitors decrease tumor growth and WT1 expression in leukemia tumor models. (A-B) 17-AAG and STA-9090 treatment at their respective HNSTDs significantly inhibited tumor growth in the MV4-11 (A) and the Kasumi-1 (B) xenograft models. In both studies, intravenous dosing was conducted 5× per week (arrowheads). STA-9090 treatment significantly inhibited tumor growth relative to vehicle in both models (*P < .05), and there was a strong trend toward STA-9090 being superior to 17-AAG in the MV4-11 model, although this difference or the difference between the 17-AAG and vehicle-treated groups did not reach statistical significance. Error bars represent ± SEM (n = 8/group). (C-D) Both compounds were well tolerated, as indicated by minimal affects on body weight loss in the MV4-11 (C) and Kasumi-1 (D) xenograft models over the course of the study. The differences in body weight changes between the vehicle- and Hsp90 inhibitor–treated groups were largely due to increasing tumor mass in the vehicle-treated animals over the course of these studies. (E) MV4-11 tumor-bearing animals were given single doses of vehicle, STA-9090 and 17-AAG, and after 6 hours, tumors were removed for Western blot analysis using anti-WT1, anti–Bcl-2, anti–c-Myc, and anti–β-actin. The expression levels of WT1, c-Myc, and Bcl-2 were significantly decreased after treatment with both Hsp90 inhibitors.

Hsp90 inhibitors decrease tumor growth and WT1 expression in leukemia tumor models. (A-B) 17-AAG and STA-9090 treatment at their respective HNSTDs significantly inhibited tumor growth in the MV4-11 (A) and the Kasumi-1 (B) xenograft models. In both studies, intravenous dosing was conducted 5× per week (arrowheads). STA-9090 treatment significantly inhibited tumor growth relative to vehicle in both models (*P < .05), and there was a strong trend toward STA-9090 being superior to 17-AAG in the MV4-11 model, although this difference or the difference between the 17-AAG and vehicle-treated groups did not reach statistical significance. Error bars represent ± SEM (n = 8/group). (C-D) Both compounds were well tolerated, as indicated by minimal affects on body weight loss in the MV4-11 (C) and Kasumi-1 (D) xenograft models over the course of the study. The differences in body weight changes between the vehicle- and Hsp90 inhibitor–treated groups were largely due to increasing tumor mass in the vehicle-treated animals over the course of these studies. (E) MV4-11 tumor-bearing animals were given single doses of vehicle, STA-9090 and 17-AAG, and after 6 hours, tumors were removed for Western blot analysis using anti-WT1, anti–Bcl-2, anti–c-Myc, and anti–β-actin. The expression levels of WT1, c-Myc, and Bcl-2 were significantly decreased after treatment with both Hsp90 inhibitors.

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