Figure 1.

Pan-ERBB inhibitors cause apoptosis in BT474 cells with acquired resistance to lapatinib. (a) MTS assays reveal a panel of kinase inhibitors that attenuate proliferation of lapatinib-sensitive (left) and -resistant (right) BT474 cells (BT474 and BT474-LR, respectively). Cells were plated at a density of 1.0 × 10⁴ per well on a 96 well plate, 18-24 hours before treatment. Cells were then treated with 1 μM of the indicated kinase inhibitors (except PD98059, U0126, and KU55933 at 10 μM). *P < 0.05 by t-test (n = 4, error bars indicate SD). (b) Lapatinib-resistant BT474 cells were treated with DMSO, lapatinib, afatinib, canertinib, dacomitinib, neratinib, or varlitinib (1 μM). Forty-eight hours later, cellular apoptosis was analyzed by Annexin V staining.