Deguelin-induced inhibition of cyclooxygenase-2 expression in human bronchial epithelial cells
Deguelin-induced inhibition of cyclooxygenase-2 expression in human bronchial epithelial cells
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DOI：
10.1158/1078-0432.ccr-0833-3
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发表时间：
2004-02-01
影响因子：
11.5
通讯作者：
Kurie, JM
中科院分区：
文献类型：
--
作者：
Lee, HY;Suh, YA;Kurie, JM
环氧合酶（考克斯）-2表达的增加显著增强了肿瘤的发生和炎症反应，其调控可能是肿瘤化学预防的合理靶点。我们以前证明鱼藤素通过调节参与考克斯-2表达的磷脂酰肌醇-3-激酶Akt活性来抑制癌前人类支气管上皮（HBE）细胞（如1799细胞和鳞状HBE细胞）的增殖。我们试图确定鱼藤素对鳞状HBE细胞中考克斯-2表达的影响。鱼藤素可明显抑制HBE鳞状细胞中考克斯-2的表达，但不影响考克斯-1的蛋白水平。鱼藤素通过诱导H322 NSCLC和HBE鳞状细胞凋亡抑制多种非小细胞肺癌（NSCLC）细胞系的增殖，并诱导Bax表达。鱼藤素处理不影响Bcl-2蛋白水平，但增加了HBE鳞状细胞中促凋亡蛋白p53和细胞周期蛋白依赖性激酶抑制剂p21和p27的表达水平。鱼藤素对HBE和NSCLC细胞的敏感性以及鱼藤素对HBE细胞中考克斯-2表达的抑制作用表明，调节考克斯-2的表达参与了鱼藤素的肺癌化学预防作用。
The increased expression of cyclooxygenase (COX)-2 significantly enhances carcinogenesis and inflammatory reactions, and its regulation may be a reasonable target for cancer chemoprevention. We demonstrated previously that deguelin inhibits proliferation of premalignant human bronchial epithelial (HBE) cells, such as 1799 cells and squamous HBE cells, by regulating phosphatidylinositol-3-kinase Akt activity, which is involved in COX-2 expression. We sought to determine the effect of deguelin on COX-2 expression in squamous HBE cells. Deguelin strongly inhibited COX-2 expression in squamous HBE cells, without affecting the COX-1 protein level. Deguelin inhibited proliferation of a variety of non-small cell lung carcinoma (NSCLC) cell lines through apoptosis and induced Bax expression in the H322 NSCLC and squamous HBE cells. Deguelin treatment did not affect Bcl-2 protein levels but increased expression levels of the proapoptotic protein p53 and the cyclin-dependent kinase inhibitors p21 and p27 in the squamous HBE cells. The sensitivity of the squamous HBE and NSCLC cells to deguelin and the inhibitory effects of deguelin on COX-2 expression in the squamous HBE cells indicate that regulation of COX-2 expression is involved in the chemopreventive action of deguelin in lung cancer.