Nahta Rita, Hung Mien-Chie, Esteva Francisco J
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Cancer Res. 2004 Apr 1;64(7):2343-6. doi: 10.1158/0008-5472.can-03-3856.
Trastuzumab (herceptin) and pertuzumab (Omnitarg, 2C4) are recombinant humanized monoclonal antibodies that target different extracellular regions of the HER-2 tyrosine kinase receptor. We explored combination effects of these agents in the HER-2-overexpressing BT474 breast cancer cell line. Trastuzumab and 2C4 synergistically inhibited the survival of BT474 cells, in part, because of increased apoptosis. Trastuzumab increased 2C4-mediated disruption of HER-2 dimerization with the epidermal growth factor receptor and HER-3. Combination drug treatment reduced levels of total and phosphorylated HER-2 protein and blocked receptor signaling through Akt but did not affect mitogen-activated protein kinase. These results suggest that combining HER-2-targeting agents may be a more effective therapeutic strategy in breast cancer rather than treating with a single HER-2 monoclonal antibody.
曲妥珠单抗（赫赛汀）和帕妥珠单抗（Omnitarg，2C4）是重组人源化单克隆抗体，它们靶向HER-2酪氨酸激酶受体的不同细胞外区域。我们在HER-2过表达的BT474乳腺癌细胞系中探究了这些药物的联合效应。曲妥珠单抗和2C4协同抑制BT474细胞的存活，部分原因是凋亡增加。曲妥珠单抗增强了2C4介导的HER-2与表皮生长因子受体及HER-3二聚化的破坏。联合药物治疗降低了总HER-2蛋白和磷酸化HER-2蛋白的水平，并通过Akt阻断受体信号传导，但不影响丝裂原活化蛋白激酶。这些结果表明，联合使用HER-2靶向药物可能是乳腺癌中比单一使用HER-2单克隆抗体更有效的治疗策略。
