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Dig Dis Sci (2008) 53:597605 DOI 10.1007/s10620-007-9922-1
ORIGINAL PAPER
Effect of Adiponectin and Ghrelin on Apoptosis of Barrett Adenocarcinoma Cell Line
Peter C. Konturek Grzegorz Burnat Tilman Rau Eckhart G. Hahn Stanislaw Konturek
Received: 27 February 2007 / Accepted: 4 July 2007 / Published online: 1 September 2007 Springer Science+Business Media, LLC 2007
Abstract Background Obesity is an important risk factor for Barrett adenocarcinoma. However, the role of adiponectin (anti-inammatory adipokine from adipose tissue) and ghrelin (orexigenic peptide gastric origin) on the progression of Barretts carcinogenesis has not been investigated so far. The aim of the present study was: (1) to compare the expression of adiponectin and ghrelin receptors in Barretts esophagus and in normal squamous epithelium; (2) to assess the effect of adiponectin and ghrelin on apoptosis in Barretts adenocarcinoma cells in vitro; and (3) to investigate the effect of ghrelin on IL-1b and COX-2 expression in OE-19 cells incubated with TNFa. Methods The expression of ghrelin and adiponectin receptors (GHS-R1a, Adipo-R1, Adipo R-2) in biopsies from Barretts esophagus and in Barretts adenocarcinoma cell line OE-19 was assessed by quantitative RT-PCR (qRT-PCR). The OE-19 cells were also incubated with adiponectin (510 lg/ml), and the apoptosis and proliferation were assessed by FACS and MTT assays. Additionally, effects of adiponectin on the mRNA and protein expression of proapoptotic Bax and antiapoptotic Bcl-2 were assessed by RT-PCR and Western blot, respectively. In two different in vitro models of esophagitis the OE-19 cells were incubated with ghrelin alone or in the
presence of TNFa or bile acids in the normal or pulse acidied medium, and the expression of IL-1b and COX-2 as markers for inammation were assessed by FACS and qRT-PCR, respectively. Results Adiponectin caused a signicant increase in apoptosis, and this affect was accompanied by increased Bax and decreased Bcl-2 expression. In contrast, ghrelin had no effect on apoptosis of OE-19 cells incubated in neutral or acidied medium with or without addition of deoxycholic acid. At the mRNA level, the expression of adiponectin receptors (Adipo-R1, Adipo-R2) was decreased, and the expression of ghrelin receptor (GHS-R1a) was increased in Barretts mucosa. Ghrelin caused a decrease in TNFa-induced COX-2 and IL-1b expression in OE-19 cells. Conclusion Adiponectin and ghrelin have an inhibitory effect on Barretts carcino-genesis by two...