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Andrea Alimonti, Caterina Nardella, Zhenbang Chen, John G. Clohessy, Arkaitz Carracedo, Lloyd C. Trotman, Ke Cheng, Shohreh Varmeh, Sara C. Kozma, George Thomas, Erika Rosivatz, Rudiger Woscholski, Francesco Cognetti, Howard I. Scher, Pier Paolo Pandolfi
Published in Volume 120, Issue 3
J Clin Invest. 2010; 120(3):681–693 doi:10.1172/JCI40535
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Figure 5
Nutlin-3 potentiates senescence and acts synergistically to RAD001 in restricting tumorigenesis in vivo.

(A) Schematic representation of the timing of drug administration in the different treatment groups (n = 10 for each group). sac, sacrifice. (B) Sizes of the anterior prostate in Ptenpc–/– mice (8 weeks of age) after the indicated treatments. (C) Quantification of the anterior prostates (APs) size and number of PIN-affected glands in mice (n = 6 for each treatment group) treated with the indicated drugs. Error bars show SD. P indicates the statistical significance (untreated versus each group of treatments). (D) Histopathological analysis and senescence of 8-week-old prostate tumors after treatments and staining as indicated: H&E, pS6, β-gal, p53, and Ki-67. Insets in H&E, pS6, p53, and Ki-67 represent a WT control stained as indicated (original magnification, ×20). (E) Quantification of the β-gal staining in anterior prostate sections of mice treated as indicate Representative sections from 3 mice were counted for each treatment group. Sections were counterstained with DAPI staining for β-gal quantification. (F) Quantification of p53 in the anterior prostate sections of mice treated as indicated. Sections from 3 mice were counted for each treatment group. (G) Quantification of Ki-67 staining in anterior prostates of mice treated as indicated and quantified as in E. (H) Quantification of TUNEL assay for apoptosis in the anterior prostates of mice treated as indicated (more than 3 mice per treatment group). Error bars in EH represent SD for a representative experiment performed in triplicate. (I) Summary of the molecular pathway and pharmacological manipulation of PI3K pathway for pro-senescence therapy for cancer.