Shiraz University of Medical Sciences, Shiraz, Iran.
Oncol Res. 2013;20(8):333-40. doi: 10.3727/096504013X13657689382734.
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 30% of patients with breast cancer. HER2 targeting is the mainstay of targeted therapy for the treatment of invasive breast cancers. Due to biological and therapeutic advantages, single chain fragment variable (scFv) antibodies have emerged as promising alternative therapeutics. In this study, we assessed the capability of three scFvs against HER2 extracellular domains (II, III, IV) in deregulation of some key signaling mediators that have important roles in growth, survival, angiogenesis, and cell migration of breast tumor cells. Downregulation of activated Akt (p-Akt), increase of p27 protein levels, and downregulation of HER1, HER2, HER3 and epidermal growth factor (EGF), CXCR3, CXCL10, and MMP2 were observed following treatment of breast cancer cells (SKBR3 cell line) with the scFvs and their combination. Our results suggest that the combination of the three scFvs could be considered as an effective cocktail on HER2 tumorgenic signaling pathways that leads to tumor growth suppression and death.
人表皮生长因子受体 2（HER2）在 30%的乳腺癌患者中过表达。HER2 靶向治疗是治疗浸润性乳腺癌的主要靶向治疗方法。由于具有生物学和治疗学优势，单链片段可变区（scFv）抗体已成为很有前途的替代治疗方法。在这项研究中，我们评估了针对 HER2 细胞外结构域（II、III、IV）的三种 scFv 调节一些关键信号转导介质的能力，这些介质在乳腺癌细胞的生长、存活、血管生成和细胞迁移中发挥重要作用。用 scFv 及其组合处理乳腺癌细胞（SKBR3 细胞系）后，观察到活化的 Akt（p-Akt）下调、p27 蛋白水平增加以及 HER1、HER2、HER3 和表皮生长因子（EGF）、CXCR3、CXCL10 和 MMP2 的下调。我们的结果表明，三种 scFv 的组合可被视为针对 HER2 致癌信号通路的有效鸡尾酒疗法，可导致肿瘤生长抑制和死亡。
