Abstract 1100: Correlation of basic fibroblast growth factor and cyclooxygenase-2 activity in non-small lung cancer cells

Abstract

Abstract Basic fibroblast growth factor (FGF-2) is a potent wide-spectrum mitogen and the dysregulation of its expression is associated with cell proliferation and immortalization in a wide variety of tumors. Its oncogenic nature may depend, in part, on its ability to prevent apoptosis. Its antisense gene, NUDT6, encodes a novel Nudix motif protein of unknown function, and overexpression of NUDT6 is known to suppress FGF-dependent cell proliferation (Baguma-Nibasheka et al, Mol Cell Endocrinol 267:127-136, 2007). Cyclooxygenase-2 (COX-2) is a key enzyme in prostaglandin synthesis whose up-regulation has been implicated in the promotion of lung cancer. COX-2 inhibition suppresses growth and induces apoptosis in human non-small cell lung cancer (NSCLC) cells. In this study, we evaluated the hypothesis that the antitumor activity of COX-2 inhibitors in lung cancer may involve modulation of FGF-2, which is overexpressed in NSCLC. Results: FGF, NUDT6 and COX-2 are co-expressed in NSCLC cells, and FGF-2 and COX-2, but not NUDT6 messenger RNA levels, as well as cell proliferation, are decreased by serum deprivation. Selective inhibition of COX-2 suppresses FGF-2 but not NUDT6 expression, and FGF-2 knockdown negates the effect of COX-2 inhibition on cell proliferation. These findings indicate that the antitumor effects of COX-2 inhibition in NSCLC may be mediated via suppression of FGF-2. Supported by the Frostburg State University of Biology Department. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1100. doi:10.1158/1538-7445.AM2011-1100