Acid Has Antiproliferative Effects in Nonneoplastic Barrett's Epithelial Cells

作者：Linda Anne Feagins, Hui-Ying Zhang, Kathy K. Hormi-Carver, Mizael H Quinones, Deena Thomas, Xi Zhang, Lance S. Terada, Stuart Jon Spechler, Ruben D. Ramirez, Rhonda Frances Souza · 发表于：The American Journal of Gastroenterology · 年份：2007 · DOI：10.1111/j.1572-0241.2006.01005.x · 被引用次数：53 · 研究领域：Esophageal Cancer Research and Treatment、Esophageal and GI Pathology、Gastroesophageal reflux and treatments

OBJECTIVES: For patients with Barrett's esophagus, physicians commonly prescribe antisecretory medications in dosages above those required to heal reflux esophagitis because acid has been shown to have proproliferative and antiapoptotic effects on Barrett's cancer cells and on Barrett's mucosal explants. For a number of reasons, these model systems may not be ideal for determining the effects of acid on benign Barrett's epithelial cells, however. We studied the effects of acid on proliferation and apoptosis in a nonneoplastic, telomerase-immortalized Barrett's epithelial cell line. METHODS: Barrett's cells were treated with two 3-minute exposures to acidic media. Cell growth was determined using cell counts, proliferation was studied by flow cytometry, cell viability was determined by trypan blue staining, and apoptosis was assessed by TUNEL and Annexin V. The expression levels of p53 and p21 were determined by Western blotting. p53 siRNA was used to study the effect of p53 inhibition on total cell numbers after acid exposure. RESULTS: Acid exposure significantly decreased total cell numbers at 24 h without affecting either cell viability or apoptosis. Acid exposure resulted in cell cycle prolongation that was associated with greater expression of p53, but not p21. The acid-induced decrease in total cell numbers was abolished by p53 RNAi. CONCLUSIONS: Acid exposure has p53-mediated, antiproliferative effects in nonneoplastic Barrett's epithelial cells. These findings contradi...