Adenovirus-uteroglobin suppresses COX-2 expression via inhibition of NF-κB activity in lung cancer cells

Abstract

Uteroglobin (UG, Clara cell secretory protein) is a steroid inducible, multifunctional protein that is secreted by the mucosal epithelia. UG has anti-proliferative and anti-metastatic effects in cancer cells. COX-2, which catalyzes the first step in the synthesis of prostanoids, has been shown to be overexpressed in tumors. This study investigated the effect of UG on the inhibition of COX-2 expression in lung cancer cells. The level of the COX-2 protein and its mRNA were decreased by UG, as demonstrated by Western Not and the RT-PCR, respectively. The EIA shows that UG suppressed PGE2 synthesis. Western blot showed that the NF-kappa B nuclear translocation was inhibited by the transduction of UG. In addition, an EMSA demonstrated the inhibition of the NF-kappa B-DNA binding by UG. The Luciferase assay showed that UG also inhibited the NF-kappa B-mediated transcription activity. Furthermore, transfection of the lung cancer cell lines with the COX-2 reporter gene constructs demonstrated that the transcription of COX-2 gene was suppressed by UG. These results show that the inhibition of COX-2 expression by UG transduction correlated with the suppression of NF-kappa B activity in the Lung cancer cells. This suggests that UG have the possibility for the treatment of lung cancer. (c) 2004 Published by Elsevier Ireland Ltd.