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. Author manuscript; available in PMC: 2009 Jun 1.
Published in final edited form as: Nat Med. 2008 Nov 30;14(12):1351–1356. doi: 10.1038/nm.1890

Figure 2. NVP-BEZ235 downregulates PI3K signaling in p110-α H1047R induced lung tumors and leads to rapid tumor regression.

Figure 2

(a) PIK3CA H1047R /CCSP-rtTA umors were induced in mice by feeding a doxy diet (verified by MR imaging). Mice with established tumors were treated with one dose of NVP-BEZ235 (35mg/kg) and the lungs were harvested 8 hours later. Sections were stained with the indicated antibodies. No primary was used as a control. Scale is 50 μM. (b) Tet-op PIK3CA H1047R /CCSP-rtTA mice were treated with doxycycline until tumors developed. These tumors were imaged by both PET and CT scans (top and lower panels respectively). The mice were then treated with NVP-BEZ235 35mg/kg per day for four days and underwent repeat imaging. Red arrows on the CT scans indicate tumor, and H: Heart. Scale is 5 mm. (c) PIK3CA H1047R /CCSP-rtTA mice were treated with doxy until they developed tumors (confirmed by MRI). Mice with established tumors were treated with NVP-BEZ235 35mg/kg for 3 days (left and middle) or 2 days (right) and the lungs were examined histologically. Scale is 200μM and 50μM for upper and lower panels respectively. (d,e) PIK3CA H1047R /CCSP-rtTA mice with established tumors were treated with either placebo, NVP-BEZ235 35mg/kg or rapamycin 6 mg/kg daily for 2 weeks. (d) A representative MRI is shown before and after treatment for each group. Scales is 4.5 mm. (e) The average tumor volumes of three mice in each treatment group after 2 weeks are shown relative to pretreatment tumor volumes.