Figure 4.

Pitavastatin does not synergize with AKT inhibition in ER-positive breast cancer cells. A, ER-positive breast cancer cell lines (T47D, MCF7, and BT474) were treated with increasing doses of GDC-0068 (0–2 µmol/L) or AZD5363 (T47D, 0–2 µmol/L; MCF7, 0–5 µmol/L; BT474, 0–2 µmol/L) and pitavastatin (0–2,000 nmol/L) for 72 hours, and cell density was measured by SRB assay. Data are represented as mean ± SD (N = 3 technical replicates). B, Parental and fulvestrant-resistant T47D cells were treated with increasing doses of GDC-0068 (0–5 µmol/L) or AZD5363 (0–5 µmol/L) and pitavastatin (0–2,000 nmol/L) for 72 hours, and cell density was measured by SRB assay (N = 1 technical replicate). C, Log₂-fold change in AKT inhibitor IC₅₀ (GDC-0068, AZD5363, MK2206, and ARQ 092) with 2 vs. 0 µmol/L pitavastatin was calculated for six TNBC and five ER-positive breast cancer cell lines. Data are represented around the median (N = the number of cell line and AKT inhibitor combinations tested). Statistical analysis was performed for the 2 µmol/L pitavastatin conditions using an unpaired, nonparametric Mann–Whitney test (P < 0.0001).