Abstract
Esophageal adenocarcinoma is an aggressive malignancy generally diagnosed after metastatic spread and currently lacks effective medical therapy. Expression of intracellular adhesion molecule-1 (ICAM-1) is an adverse prognostic indicator in various human tumor cells and contributes significantly to their metastatic potential. Statin therapy reduces circulating ICAM-1 levels in patients with coronary heart disease and is associated with reduction in progression from Barrett esophagus to esophageal adenocarcinoma. We hypothesize that statin therapy may attenuate growth and malignant potential via ICAM-1 expression and nuclear factor-kappa beta activation in human esophageal adenocarcinoma cells. Verified human esophageal adenocarcinoma cells (FLO-1) were treated with simvastatin, atorvastatin, or pravastatin (10-, 30-, and 50-μmol/L concentrations). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide viability, 5-bromo-2'-deoxyuridine proliferation, or annexin V apoptosis assays were performed, or cells were stimulated with tumor necrosis factor-alpha and collected for immunoblotting and flow cytometry. Simvastatin decreased cell viability and proliferation while increasing apoptosis in a dose-dependent manner (P < .05). Simvastatin attenuated total cellular and cell-surface ICAM-1 expression as well as nuclear factor-kappa beta activation (P < .05). Atorvastatin had mild effects and pravastatin had essentially no effect on growth and metastatic potential of these cells. We demonstrate that treatment of human esophageal adenocarcinoma cells with simvastatin attenuates growth, by decreasing cell viability, decreasing cell proliferation, and increasing apoptosis, and attenuates metastatic potential, by decreasing expression of key metastatic markers. These findings identify simvastatin as a potential therapeutic and chemopreventive modality to thwart the progression of esophageal adenocarcinoma.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: The Journal of Thoracic and Cardiovascular Surgery
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.