Figure 1.

MM-121 enhances trastuzumab-mediated inactivation of Akt and growth inhibition in two erbB2+ breast cancer cell lines. A, SKBR3 and BT474 breast cancer cells were untreated or treated with either trastuzumab or MM-121 alone, or their combinations for 24 hrs. Cells were collected and subjected to western blot analyses of P-erbB2, erbB2, P-erbB3, erbB3, P-Akt, Akt, P-MAPK, MAPK, or β-actin. B, SKBR3 and BT474 cells were plated onto 96-well plates and incubated at 37°C with 5% CO2. After 24 hrs, the culture medium was replaced with 0.1 ml fresh medium containing 0.5% FBS or the same medium containing the indicated concentrations of trastuzumab in the absence (Trast) or presence (Trast + MM-121) of MM-121 (10 μg/ml) for another 72 hrs. The percentages of surviving cells from each cell line relative to controls, defined as 100% survival, were determined by reduction of MTS. Bars, SD. Data show a representative of three independent experiments.