Figure 6
Simultaneous pharmacological targeting of androgen receptor (AR) and PI3K decreases viability of AR + triple-negative breast cancer (TNBC) cell lines grown in 3-dimensional suspension culture or in vivo as xenograft tumors. (A) Bright field images display 3-dimensional cell aggregates of MDA-MB-453 cells treated with increasing doses of GDC-0941 or GDC-0980 in the absence or presence of CDX (25 μM). (B) Line graphs display relative viability of 3-dimensional cell aggregates treated with GDC-0941 or GDC-0980 alone (blue) or in combination (red) with 25 μM bicalutamide (CDX). Dashed black line depicts the theoretical line of additivity determined from the effect of CDX alone and either GDC-0941 or GDC-0980 alone. (C) Athymic nude mice bearing established xenograft tumors from AR + TNBC cell lines (MDA-MB-453 and CAL-148) were divided into equal cohorts (n = 8) treated with either CDX (100 mg/kg/d, black hashed line), GDC-0941 (100 mg/kg/d, blue line), GDC-0980 (7.5 mg/kg/d red line) or with the combination of CDX and either GDC0-0941 (blue hashed line) or GDC-0980 (red hashed line). Serial-tumor volumes (mm3) were measured at the indicated days. Each data point represents mean tumor volume of 16 tumors; error bars represent standard error of the mean.