University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
J Surg Res. 2021 Mar;259:562-568. doi: 10.1016/j.jss.2020.10.018. Epub 2020 Nov 28.
Gastroesophageal reflux and Barrett's esophagus are significant risk factors for the development of esophageal adenocarcinoma. Group IIa secretory phospholipase A (sPLA) catalyzes the production of various proinflammatory metabolites and plays a critical role in promoting reflux-induced inflammatory changes within the distal esophagus. We hypothesized that inhibition of sPLA in human Barrett's cells would attenuate adhesion molecule expression via decreased activation of nuclear factor kappa B (NF-κB) and decrease cell proliferation, possibly mitigating the invasive potential of Barrett's esophagus.
Normal human esophageal epithelial cells (HET1A) and Barrett's cells (CPB) were assayed for baseline sPLA expression. CPB cells were treated with a specific inhibitor of sPLA followed by tumor necrosis factor-α. Protein expression was evaluated using immunoblotting. Cell proliferation was assessed using an MTS cell proliferation assay kit. Statistical analysis was performed using the Student's t-test or analysis of variance, where appropriate.
CPB cells demonstrated higher baseline sPLA expression than HET1A cells (P = 0.0005). Treatment with 30 μM sPLA inhibitor significantly attenuated intercellular adhesion molecule-1 (P = 0.004) and vascular cell adhesion molecule-1 (P < 0.0001) expression as well as decreased NF-κB activation (P = 0.002). sPLA inhibition decreased cell proliferation in a dose-dependent manner (P < 0.001 for 15, 20, and 30 μM doses).
sPLA inhibition in human Barrett's cells decreases cellular adhesive properties and NF-κB activation as well as decreases cell proliferation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA inhibition as a potential chemopreventive target for premalignant lesions of the esophagus.
胃食管反流和 Barrett 食管是食管腺癌发展的重要危险因素。IIa 组分泌型磷脂酶 A（sPLA）催化各种促炎代谢物的产生，并在促进远端食管反流诱导的炎症变化中发挥关键作用。我们假设，在人类 Barrett 细胞中抑制 sPLA 可通过减少核因子 kappa B（NF-κB）的激活来减轻粘附分子的表达，并减少细胞增殖，从而可能减轻 Barrett 食管的侵袭潜能。
测定正常的人食管上皮细胞（HET1A）和 Barrett 细胞（CPB）的 sPLA 基础表达。用 sPLA 的特异性抑制剂处理 CPB 细胞，然后用肿瘤坏死因子-α处理。使用免疫印迹法评估蛋白质表达。使用 MTS 细胞增殖测定试剂盒评估细胞增殖。使用学生 t 检验或适当的方差分析进行统计分析。
CPB 细胞的 sPLA 基础表达高于 HET1A 细胞（P = 0.0005）。用 30μM sPLA 抑制剂处理可显著减弱细胞间粘附分子-1（P = 0.004）和血管细胞粘附分子-1（P < 0.0001）的表达，并降低 NF-κB 激活（P = 0.002）。sPLA 抑制以剂量依赖性方式降低细胞增殖（15、20 和 30μM 剂量时 P < 0.001）。
在人类 Barrett 细胞中抑制 sPLA 可降低细胞的粘附特性和 NF-κB 激活，并减少细胞增殖，这表明炎症反应的下调和细胞恶性潜能的可能衰减。这些发现确定了 sPLA 抑制作为食管癌前病变的潜在化学预防靶点。
Zotero 插件