Lept in synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture
Lept in synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture
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DOI：
10.1016/j.mce.2007.05.017
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发表时间：
2007-08-15
影响因子：
4.1
通讯作者：
Ogunwobi, Orunseun O.
中科院分区：
文献类型：
--
作者：
Beales, Ian L. P.;Ogunwobi, Orunseun O.
肥胖和胃食管反流是食管腺癌的主要易感因素。我们研究了短暂的酸暴露和瘦素对OE 33食管腺癌细胞的影响。瘦素和酸单独刺激增殖和抑制凋亡和组合是协同的。瘦素受体蛋白水平不变的酸暴露。考克斯-2抑制剂NS 398可以阻断酸和瘦素的作用，但尽管酸和瘦素单独显着增加PGE 2的产生和考克斯-2 mRNA水平，但组合并不比单独使用任何一种兴奋剂更有效。瘦素协同增强酸刺激的EGFR和ERK磷酸化，但没有进一步增加JNK或p38 MAP激酶磷酸化。特异性EGFR和ERK抑制剂降低了瘦素和酸单独和联合的作用。肥胖者循环中瘦素水平的增加和胃酸的短暂反流的结合可能通过增加增殖和抑制凋亡促进食管癌的发生。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Obesity and gastro-oesophageal reflux are the main predisposing factors for oesophageal adenocarcinoma. We have examined the effects of transient acid exposure and leptin on OE33 oesophageal adenocarcinoma cells. Leptin and acid individually stimulated proliferation and inhibited apoptosis and the combination was synergistic. Leptin receptor protein levels were unchanged by acid exposure. The COX-2 inhibitor NS 398 blocked the effects of acid and leptin but while both acid and leptin individually significantly increased PGE2 production and COX-2 mRNA levels, the combination was not more effective than either stimulant alone. Leptin synergistically enhanced acid-stimulated EGFR and ERK phosphorylation but did not further increase JNK or p38 MAP kinase phosphorylation. Specific EGFR and ERK inhibitors reduced the effects of leptin and acid alone and in combination. The combination of increased circulating leptin levels in obesity and transient reflux of gastric acid may promote oesophageal carcinogenesis by increasing proliferation and inhibiting apoptosis. (c) 2007 Elsevier Ireland Ltd. All rights reserved.