Figure 4

Perhexiline inhibits breast cancer cell proliferation and functions synergistically with lapatinib. (A-B) MDA-MB-468 (A) and SK-BR-3 (B) cells were treated with different concentrations of perhexiline for 72 hours, and cell viability was measured using the MTS assay. Each experimental point was performed in triplicate, and results represent mean ± SEM of three independent experiments. (C) The synergistic effect of perhexiline and lapatinib on inhibiting HER3-mediated Akt signaling. MDA-MB 468 cells treated with 5 μM perhexiline alone or in combination with 100 nM lapatinib for 2 or 36 hours. Cell lysates were analyzed for the phosphorylation status of endogenous HER3 and Akt as well as total HER3 and Akt expression. (D-E) Perhexiline and lapatinib synergistically inhibit MDA-MB-468 (D) and SK-BR-3 (E) cell growth. Cells were treated with increasing concentrations of perhexiline and lapatinib alone or in combination for 72 hours. MTS assays were performed to measure cell viability. Values are expressed as a percentage of DMSO-treated cells. Results are presented as the mean ± SEM. Combinational index (CI) quantifies the degree of synergism in a drug combination. CI is obtained using the method of Chou and Martin in the software CompuSyn. CI <1 indicates drug synergy. ED50, ED75, ED90 and ED95 are the effective doses at which 50%, 75%, 90% and 95% cells are killed, respectively. DMSO, dimethyl sulfoxide; HER3, human epidermal growth factor receptor 3; SEM, standard error of the mean.