Bile salts induce or blunt cell proliferation in Barrett's esophagus in an acid-dependent fashion
Bile salts induce or blunt cell proliferation in Barrett's esophagus in an acid-dependent fashion
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DOI：
10.1152/ajpgi.2000.278.6.g1000
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发表时间：
2000-06-01
影响因子：
4.5
通讯作者：
Triadafilopoulos, G
中科院分区：
文献类型：
--
作者：
Kaur, BS;Ouatu-Lascar, R;Triadafilopoulos, G
巴雷特食管（BE）是由酸和胆汁反流引起的，易患癌症。我们研究了胆汁盐（含或不含酸）对BE细胞增殖的影响，并评估了相关机制。为了模拟生理条件，将食管、BE和十二指肠的活检组织暴露于胆盐混合物，连续或以1小时脉冲的方式，并与不含胆盐的对照培养基（pH 7.4）进行比较，持续时间小于或等于24小时。类似的实验也进行了酸化介质（pH 3.5）与胆汁盐混合物作为1小时脉冲。通过[H-3]胸苷掺入试验评估细胞增殖，有或没有双吲哚马来酰亚胺（BIM），一种选择性蛋白激酶C抑制剂。胆盐脉冲增强BE中的细胞增殖，而不影响食管或十二指肠上皮细胞的增殖。在BIM的存在下，有完全闭塞的胆汁盐诱导的BE过度增殖。与此相反，1小时脉冲的胆盐结合酸显着抑制增殖BE，但对食管或十二指肠没有影响。我们得出结论，在BE外植体，短暂暴露于胆汁盐，在没有酸的情况下，增加增殖，而暴露于胆汁盐和酸的组合一起抑制增殖。
Barrett's esophagus (BE) results from acid and bile reflux and predisposes to cancer. We investigated the effect of bile salts, with or without acid, on cell proliferation in BE and assessed mechanism(s) involved. To mimic physiological conditions, biopsies of esophagus, BE, and duodenum were exposed to a bile salt mixture, either continuously or as a 1-h pulse, and were compared with control media without bile salts (pH 7.4) for less than or equal to 24 h. Similar experiments were also performed with acidified media (pH 3.5) combined with the bile salt mixture as a 1-h pulse. Cell proliferation was assessed by a [H-3]thymidine incorporation assay with or without bisindolylmaleimide (BIM), a selective protein kinase C inhibitor. Bile salt pulses enhanced cell proliferation in BE without affecting cell proliferation in esophageal or duodenal epithelia. In the presence of BIM, there was complete obliteration of the bile salt-induced BE hyperproliferation. In contrast, 1-h pulses of bile salts in combination with acid significantly inhibited proliferation in BE but had no effect on esophagus or duodenum. We conclude that in BE explants, brief exposure to bile salts, in the absence of acid, increases proliferation, whereas exposure to a combination of bile salts and acid together inhibits proliferation.