Figure 2.

MM-121 significantly enhances trastuzumab-induced growth inhibition in two otherwise resistant cell lines correlated with inactivation of the erbB3/PI-3K/Akt signaling. A, SKBR3-pool2 and BT474-HR20 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. B, SKBR3-pool2 and BT474-HR20 cells were untreated or treated with either trastuzumab or MM-121 alone, or their combinations for 24 or 48 hrs. Cells were collected and subjected to western blot analyses with the indicated antibodies.