Gene silencing of β-catenin by RNAi inhibits cell proliferation in human esophageal cancer cells in vitro and in nude mice

Abstract

β-catenin, which is frequently overexpressed in a variety of human cancers including esophageal cancer, mediates cancer cell proliferation and tumor growth. In the present study, we used a human U6 promoter-driven DNA-template approach to induce short hairpin RNA (shRNA)-triggered RNA interference to silence β-catenin gene expression in human esophageal squamous cell carcinoma cell line Eca-109, and then evaluated its effects on the proliferation and growth of tumor cells in vitro and in nude mice. β-catenin expression levels decreased markedly in Eca-109 cells transfected with a plasmid expressing shRNA for β-catenin. Downregulation of β-catenin was concomitantly accompanied by reduction of cyclin D1, colony formation, and growth inhibition of Eca-109 cells in vitro. The mechanism appears to be the G0/G1 phase arrest but not induction of apoptosis. In vivo, treatment of Eca-109 cells with β-catenin shRNA greatly impeded tumor growth in nude mice. We conclude that plasmid vector-mediated β-catenin RNA interference holds great promise as a novel treatment on human esophageal cancer with β-catenin overexpression. © 2009 International Society for Diseases of the Esophagus.