Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Cell Oncol (Dordr). 2012 Jun;35(3):149-61. doi: 10.1007/s13402-012-0076-6. Epub 2012 Apr 3.
Barrett's esophagus (BE) is a premalignant condition caused by chronic gastroesophageal reflux. BE patients have an increased risk of developing esophageal adenocarcinoma (EAC). As many aspects of this condition are still unknown, there is a need for in vitro models to study BE development.
To review the literature on cell lines and incubation conditions for studying BE development.
A literature search was performed using PubMed, EMBASE and the Cochrane library, combining the words esophagus, cell line, culture, Barrett's, bile, acid, exposure, reflux and adenocarcinoma.
A wide range of cell lines and incubation conditions to study BE development have been reported. The most commonly used cell lines are derived from epithelium from patients with BE or EAC. A 25-minute incubation with 200 μM bile salts induced cell proliferation and Akt phosphorylation. However, increased CDX2 and MUC2 expression was only observed with longer incubations or higher bile salt concentrations. Two-hundred μM bile at pH 6 showed a higher toxicity to EAC cells than the same concentration at pH 7. Multiple 5-minute exposures with 200 μM bile at pH 4 or pH 7 increased CK8/18 and COX2 in BE epithelial cells.
Two-hundred μM conjugated primary or secondary bile salts at pH 4 for multiple short exposures is able to induce BE specific factors in BE cell lines. In SQ and EAC cell lines; however, higher concentrations of secondary bile salts for 8 h are needed to induce BE specific molecules. Due to the high variability in reported methods, it is difficult to determine the most effective in vitro setup for studying the development of BE.
巴雷特食管（BE）是一种由慢性胃食管反流引起的癌前病变。BE 患者发生食管腺癌（EAC）的风险增加。由于这种情况的许多方面仍然未知，因此需要体外模型来研究 BE 的发展。
综述用于研究 BE 发展的细胞系和孵育条件的文献。
通过使用 PubMed、EMBASE 和 Cochrane 图书馆进行文献检索，结合食管、细胞系、培养、巴雷特、胆汁、酸、暴露、反流和腺癌等关键词进行检索。
已经报道了广泛用于研究 BE 发展的细胞系和孵育条件。最常用的细胞系来自 BE 或 EAC 患者的上皮细胞。25 分钟孵育 200μM 胆盐可诱导细胞增殖和 Akt 磷酸化。然而，只有较长孵育时间或较高胆盐浓度才能观察到 CDX2 和 MUC2 表达增加。pH6 时 200μM 胆汁对 EAC 细胞的毒性高于 pH7 时相同浓度的胆汁。pH4 或 pH7 时，200μM 胆汁进行多次 5 分钟暴露可增加 BE 上皮细胞中的 CK8/18 和 COX2。
pH4 时多次短时间暴露 200μM 结合初级或次级胆盐可诱导 BE 细胞系中出现 BE 特异性因子。然而，在 SQ 和 EAC 细胞系中，需要更高浓度的次级胆盐（8h）才能诱导出现 BE 特异性分子。由于报道方法的高度可变性，很难确定用于研究 BE 发展的最有效体外设置。
