The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action
The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action
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DOI：
10.1016/s0959-8049(99)00333-0
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发表时间：
2000-03-01
影响因子：
8.4
通讯作者：
Hull, MA
中科院分区：
文献类型：
--
作者：
Smith, ML;Hawcroft, G;Hull, MA
非甾体抗炎药(NSAIDs)在体外抑制人结直肠癌细胞的增殖和诱导其凋亡。目前尚不清楚非类固醇抗炎药是否通过抑制环氧合酶-2(COX-2)发挥作用，以及非类固醇抗炎药如何发挥抗增殖作用。我们研究了选择性COX-2抑制剂NS-398、非选择性COX抑制剂吲哚美辛和阿司匹林对四种人结直肠癌细胞株HT29.Fu、Hca-7、SW480和HCT116的作用。NS-398可完全抑制表达COX-2的细胞(HT29.Fu和Hca-7)的增殖，诱导其G1期停滞，促进细胞凋亡。然而，无论COX-2表达如何，吲哚美辛对所有细胞都有类似的作用。NS-398对COX-2阴性细胞株(SW480和HCT116)也具有抗增殖作用。阿司匹林可抑制所有细胞系的增殖，但不能诱导细胞凋亡。消炎痛降低了所有细胞中β-连环蛋白的表达(与NS-398或阿司匹林不同)。非甾体抗炎药通过不同的机制作用于人结直肠癌细胞。β-连环蛋白表达降低可能参与了消炎痛的抗增殖作用。(C)2000爱思唯尔科学有限公司。保留所有权利。
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and induce apoptosis in human colorectal cancer cells in vitro. It remains unclear whether individual NSAIDs act by cyclooxygenase-2 (COX-2) inhibition and how NSAIDs exert their antiproliferative effects. We investigated the effects of NS-398 (a selective COX-2 inhibitor), indomethacin (a non-selective COX inhibitor) and aspirin on four human colorectal cancer cell lines (HT29.Fu, HCA-7, SW480 and HCT116). NS-398 completely inhibited proliferation, induced G1 arrest and promoted apoptosis in COX-2-expressing cells (HT29.Fu and HCA-7). However, indomethacin had similar effects on all cells, regardless of COX-2 expression. NS-398 also had anti-proliferative activity on COX-2-negative cell lines (SW480 and HCT116). Aspirin inhibited proliferation of all cell lines but did not induce apoptosis. Indomethacin decreased beta-catenin protein expression in all cells (unlike NS-398 or aspirin). NSAIDs act on human colorectal cancer cells via different mechanisms. Decreased beta-catenin protein expression may mediate the anti-proliferative effects of indomethacin. (C) 2000 Elsevier Science Ltd. All rights reserved.