The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells
The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells
复制标题
DOI：
10.1158/0008-5472.can-03-3856
复制
发表时间：
2004-04-01
期刊：
影响因子：
11.2
通讯作者：
Esteva, FJ
中科院分区：
文献类型：
--
作者：
Nahta, R;Hung, MC;Esteva, FJ
曲妥珠单抗（赫赛汀）和帕妥珠单抗（Omnitarg，2C 4）是重组人源化单克隆抗体，靶向HER-2酪氨酸激酶受体的不同细胞外区域。我们探讨了这些药物在HER-2过表达的BT474乳腺癌细胞系中的联合作用。曲妥珠单抗和2C 4协同抑制BT474细胞的存活，部分原因是细胞凋亡增加。曲妥珠单抗增加2C 4介导的HER-2与表皮生长因子受体和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，阻断了通过Akt的受体信号传导，但不影响丝裂原活化蛋白激酶。这些结果表明，与单一HER-2单克隆抗体治疗相比，联合HER-2靶向药物可能是乳腺癌更有效的治疗策略。
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.