Fig. S7.
Quantitative analysis of mitosis and apoptosis in response to PI3K and PARP inhibition after 3 d of treatment. Tumor-bearing mice were prepared and treated as described in Fig. 4A. For each treatment category, a minimum of two animals were killed at 72 h to determine biomarker responses. Immunohistochemistry was performed with antibodies against Ki67 (A) and CC3 (B), and three to five images were taken at 40x and analyzed with volocity software. (C) Effects of phenformin on treatment responses of a K14-Cre BRCA1f/fp53f/f tumor with acquired resistance to BKM120 and Olaparib. Tumors were implanted, allowed to grow to a size of 5 mm, and randomized to treatments with vehicle control (n = 2), BKM120 and Olaparib, or BKM120+Olaparib+Phenformin (n = 3). Tumors were assessed at the time points indicated. Tumor growth retardation with addition of Phenformin was significant between days 10 and 21 (P < 0.05).