Deregulation of HER2 downstream signaling in breast cancer cells by a cocktail of anti-HER2 scFvs

摘要

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.