Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells.
Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells.
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DOI：
10.1038/sj.bjc.6601901
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发表时间：
2004-07-05
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
人结直肠癌 (CRC) 细胞中 β-连环蛋白水平升高会导致“促肿瘤”β-连环蛋白/T 细胞因子 (TCF) 靶基因（例如细胞周期蛋白 D1）的反式激活增加。因此，非甾体类抗炎药（NSAID）抗CRC活性的可能靶点是β-连环蛋白和连环蛋白相关转录（CRT）。我们测试了一组 NSAID（吲哚美辛、双氯芬酸、硫化舒林酸和砜、罗非考昔；范围 10-600 μM）的抗增殖活性以及对 β-连环蛋白和细胞周期蛋白 D1 蛋白水平以及 CRT（使用合成 β-连环蛋白/TCF 报告基因 [TOPflash] 测量）的影响。 SW480 人结直肠癌细胞体外。 NSAID 治疗后，细胞增殖减少、细胞凋亡诱导与 β-catenin 蛋白水平或 CRT 变化之间没有一致的关系。除罗非考昔外，所有 NSAID 均降低核 β-连环蛋白含量和细胞周期蛋白 D1 蛋白水平，同时具有抗增殖活性。然而，细胞周期蛋白 D1 下调发生在总 β-连环蛋白水平下降之前，并且与 CRT 的变化没有相关性，表明 NSAIDs 对细胞周期蛋白 D1 表达存在不依赖于 CRT 的影响。总之，NSAIDs 对 β-catenin 蛋白和 CRT 具有不同的影响，这不太可能完全解释它们对细胞周期蛋白 D1 的影响以及它们对体外人 CRC 细胞的抗增殖活性。
Elevated β-catenin levels in human colorectal cancer (CRC) cells lead to increased trans-activation of ‘protumorigenic’ β-catenin/T-cell factor (TCF) target genes such as cyclin D1. Therefore, possible targets for the anti-CRC activity of nonsteroidal anti-inflammatory drugs (NSAIDs) are β-catenin and catenin-related transcription (CRT). We tested the antiproliferative activity and the effects on levels of β-catenin and cyclin D1 protein, as well as CRT (measured using a synthetic β-catenin/TCF-reporter gene [TOPflash]), of a panel of NSAIDs (indomethacin, diclofenac, sulindac sulphide and sulphone, rofecoxib; range 10–600 μM) on SW480 human CRC cells in vitro. Following NSAID treatment, there was no consistent relationship between reduced cell proliferation, induction of apoptosis and changes in β-catenin protein levels or CRT. All the NSAIDs, except rofecoxib, decreased nuclear β-catenin content and cyclin D1 protein levels in parallel with their antiproliferative activity. However, cyclin D1 downregulation occurred prior to a decrease in total β-catenin protein levels and there was no correlation with changes in CRT, suggesting the existence of CRT-independent effects of NSAIDs on cyclin D1 expression. In summary, NSAIDs have differential effects on β-catenin protein and CRT, which are unlikely to fully explain their effects on cyclin D1 and their antiproliferative activity on human CRC cells in vitro.
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影响因子：
8.4
作者：
Smith, ML;Hawcroft, G;Hull, MA
通讯作者：
Hull, MA
影响因子：
5.8
作者：
Li, H;Liu, L;Thompson, WJ
通讯作者：
Thompson, WJ
影响因子：
8.8
作者：
Boon, E M J;Keller, J J;Wormhoudt, T A M;Giardiello, F M;Offerhaus, G J A;van der Neut, R;Pals, S T
通讯作者：
Pals, S T
DOI：
10.1124/jpet.103.048769
发表时间：
2003-05-01
影响因子：
3.5
作者：
Hawcroft, G;Gardner, SH;Hull, MA
通讯作者：
Hull, MA
影响因子：
3.7
作者：
Shiff, SJ;Koutsos, MI;Rigas, B
通讯作者：
Rigas, B