Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky 40202, USA.
J Surg Res. 2011 Dec;171(2):623-30. doi: 10.1016/j.jss.2010.04.038. Epub 2010 May 21.
Bile acids are implicated as etiologic agents in esophageal cancer. We sought to analyze the impact of bile acid exposure on esophageal epithelial cells, Barrett's metaplastic cells (BE), esophageal adenocarcinoma cells (EAC), and esophageal squamous carcinoma cell (ESC). We sought to determine if cellular resistance is related to manganese superoxide dismutase expression.
Cells were exposed to sodium choleate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), sodium taurocholate (TCA), or a 1:1 mixture (MIX) of reagents at concentrations in the range 0.2-0.8 mM. Cell viability was evaluated by MTT assay. Manganese superoxide dismutase (MnSOD) expression was analyzed by Western blot. Statistical analysis was performed using SPSS ver. 17.0, SPSS Inc., Chicago, IL.
Bile salt exposure inhibited cell viability in esophageal squamous cells in time- and growth-dependent manner. There was a 50% decrease in cell viability from 4 to 24 h. BE, EAC, and ESC cell lines were more resistant to bile insult. In untreated cell lines, MnSOD expression was significantly decreased in EAC and ESC cell lines compared with esophageal squamous epithelial cells and BE cells (P=0.002). Exposure of ESC cells to bile salt increased MnSOD expression.
The confirmation of the role of reactive oxygen species (ROS) and bile acids in esophageal carcinogenesis has interesting implications for chemoprevention in patients with reflux esophagitis and Barrett's esophagus. Further studies are necessary to assess the preventative role of antioxidant supplementation.
胆汁酸被认为是食管癌的病因。我们试图分析胆汁酸暴露对食管上皮细胞、巴雷特化生细胞（BE）、食管腺癌细胞（EAC）和食管鳞状细胞癌（ESC）的影响。我们试图确定细胞耐药性是否与锰超氧化物歧化酶表达有关。
细胞分别用胆酸钠（CA）、脱氧胆酸钠（DCA）、甘胆酸钠（GCA）、牛磺胆酸钠（TCA）或试剂混合物（MIX）在 0.2-0.8 mM 浓度下进行孵育。通过 MTT 试验评估细胞活力。通过 Western blot 分析锰超氧化物歧化酶（MnSOD）表达。使用 SPSS ver. 17.0 进行统计分析，SPSS Inc.，芝加哥，IL。
胆汁盐暴露以时间和生长依赖性方式抑制食管鳞状细胞活力。细胞活力从 4 小时到 24 小时下降了 50%。BE、EAC 和 ESC 细胞系对胆汁刺激的抵抗力更强。在未处理的细胞系中，EAC 和 ESC 细胞系中 MnSOD 表达明显低于食管鳞状上皮细胞和 BE 细胞（P=0.002）。ESC 细胞暴露于胆汁盐后 MnSOD 表达增加。
活性氧（ROS）和胆汁酸在食管癌发生中的作用的证实对反流性食管炎和 Barrett 食管患者的化学预防具有有趣的意义。需要进一步研究来评估抗氧化剂补充的预防作用。
