RNA interference (RNAi) is the process by which double-stranded RNA directs sequence-specific degradation of mRNA. A DNA vector-based approach has been shown to be able to trigger RNA interference in mammalian cells successfully. LRH-1 is an orphan nuclear receptor predominantly expressed in tissues of endodermal origin, where it controls development and cholesterol homeostasis. In the present study, we demonstrated that the expression of hLRH-1 and cyclin El in BEL-7402 cells could be suppressed by up to similar to 80% via DNA vector-based RNA interference. The suppression of hLRH-1 resulted in cell cycle arrest mediated by the down-regulation of cyclin E1. Induction of apoptosis and down-regulation of Gadd45 beta were also shown in hLRH-1 knock down BEL-7402 cells. These results, together with the findings that Gadd45 beta remained unchanged in cyclin El RNAi cells, suggested that the induction of apoptosis by knock down of hLRH-1 was closely related to the down-regulation of Gadd45 beta. (c) 2005 Elsevier Inc. All rights reserved.