Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: Effects on cell cycle and apoptosis
Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: Effects on cell cycle and apoptosis
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DOI：
10.1006/excr.1996.0023
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发表时间：
1996-01-10
影响因子：
3.7
通讯作者：
Rigas, B
中科院分区：
文献类型：
--
作者：
Shiff, SJ;Koutsos, MI;Rigas, B
阿司匹林和其他非甾体抗炎药降低结肠癌的发病率和死亡率，但其作用机制仍不清楚。我们评估了阿司匹林（阿萨）和其他三种结构无关的NSAID（吲哚美辛，萘普生和吡罗昔康）对HT-29结肠腺癌细胞体外细胞增殖，细胞周期时相分布和凋亡的影响。所有的NSAID检查减少了增殖，并改变了这些细胞的形态，在时间和浓度依赖性的方式。此外，它们改变了这些细胞的细胞周期时相分布。它们增加了细胞周期中G（0）/G（1）期的细胞比例，减少了S期的细胞比例。阿萨和吲哚美辛也降低了G（2）/M期细胞的百分比，而萘普生和吡罗昔康没有。与其对细胞周期的影响平行，阿萨和吲哚美辛也降低了p34（cdc 2）和p33（cdk 2）的水平，这两种细胞周期蛋白依赖性激酶对细胞周期进程很重要。最后，除阿萨外，所有分析的NSAID均诱导这些细胞凋亡。这些化合物诱导细胞凋亡的相对效力与其延缓细胞增殖的有效性之间存在粗略的相关性。我们的研究结果表明，NSAID可以在体外降低HT-29结肠癌细胞的增殖。此外，它们引起细胞周期静止和凋亡，这两者都可以解释它们的抗增殖作用。这些发现表明这些化合物在人类中的癌症预防作用的可能机制。(C)出版社：Academic Press
Aspirin and other NSAIDs reduce the incidence of and mortality from colon cancer, but their mechanism of action remains unknown. We evaluated the effect of aspirin (ASA) and three other structurally unrelated NSAIDs (indomethacin, naproxen, and piroxicam) on cell proliferation, cell cycle phase distribution, and the development of apoptosis in HT-29 colon adenocarcinoma cells in vitro. All of the NSAIDs examined reduced the proliferation and altered the morphology of these cells in a time- and concentration-dependent manner. In addition, they altered the cell cycle phase distribution of these cells. They increased the proportion of cells in the G(0)/G(1) phase and reduced the proportion in the S phase of the cell cycle. ASA and indomethacin also reduced the percentage of cells in the G(2)/M phase, whereas naproxen and piroxicam did not. Parallel to their effect on cell cycle, ASA and indomethacin also reduced the levels of p34(cdc2) and p33(cdk2), two cyclin-dependent kinases that are important for cell cycle progression. Finally, all the NSAIDs analyzed, except ASA, induced apoptosis in these cells. There was a rough correlation between the relative potency of these compounds in inducing apoptosis and their effectiveness in retarding cell proliferation, Our findings indicate that NSAIDs can reduce the proliferation of HT-29 colon cancer cells in vitro. In addition, they cause cell cycle quiescence and apoptosis, both of which could account for their anti-proliferative effect, These findings suggest possible mechanisms for the cancer preventive effects of these compounds in humans. (C) 1995 Academic Press, Inc.