Abstract
The ets‐1 transcription factor plays an important role in cell proliferation, differentiation, apoptosis and tissue remodeling. Aberrant ets‐1 expression correlates with aggressive tumor behavior and poorer prognosis in patients with various malignancies. This study evaluated the efficacy of double‐stranded decoy oligonucleotides targeting ets‐1‐binding cis elements for the suppression of ets‐1 in treatment of a peritoneal dissemination model of gastric cancer. In vitro, MTT assay was performed to evaluate the effect of the ets‐1 decoy on cell growth. Electrophoretic mobility shift assay (EMSA) was performed to determine ets‐1 activity. In vivo, the effect of the ets‐1 decoy was investigated in the peritoneal dissemination nude mice model. Disseminated nodules were analyzed immunohistochemically. Ets‐1 decoy, but not scrambled decoy, significantly inhibited cell growth in 2 gastric cancer cell lines, which showed overexpression of ets‐1 protein by inhibiting the binding activity of ets‐1. In the peritoneal dissemination model, the ets‐1 decoy significantly suppressed the disseminated nodules, and tended to prolong the survival rate. PCNA index, microvessel density and VEGF expression were also reduced in peritoneal tumors treated with ets‐1 decoy. Intraperitoneal injection of ets‐1 decoy inhibited peritoneal dissemination of gastric cancer in a nude mice model. The results indicate that the decoy strategy for ets‐1 offers a promising therapy for patients with incurable peritoneal dissemination of gastric cancer, most of which show overexpression of ets‐1 protein. © 2007 Wiley‐Liss, Inc.