Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involves β-catenin associated signaling pathway down-regulation
Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involves β-catenin associated signaling pathway down-regulation
复制标题
DOI：
10.3748/wjg.v12.i31.4981
复制
发表时间：
2006-08-21
影响因子：
4.3
通讯作者：
He, Yu-Hong
中科院分区：
文献类型：
--
作者：
He, Yu-Jun;Liu, Bao-Hua;He, Yu-Hong
目的：研究咖啡酸苯乙酯（CAPE）的抗肿瘤作用及其对SW480结直肠癌（CRC）细胞β -连环蛋白相关信号通路的影响。方法：用不同浓度的CAPE处理SW480细胞。采用甲基苯并噻唑龙（MTT）法检测细胞增殖情况。流式细胞术分析细胞周期和细胞凋亡情况。Western blotting法检测β -catenin、c-myc、cyclinD1蛋白表达水平。间接免疫荧光法测定β -连环蛋白定位。结果：CAPE对SW480细胞的生长表现出较强的抑制作用，且呈剂量和时间依赖性。FCM分析显示，CAPE作用SW480细胞24 h后，GO /G1期细胞比例升高，S期细胞比例降低，凋亡率升高。CAPE预处理SW480细胞可显著抑制β -catenin、c-myc和cyclinD1蛋白的表达。CAPE处理降低了β -连环蛋白在细胞核和细胞质中的积累，同时增加了其在细胞膜表面的积累。结论：CAPE可通过诱导细胞周期阻滞和凋亡抑制SW480细胞增殖。β -连环蛋白及其相关信号通路靶基因表达的降低可能介导CAPE的抗肿瘤作用。(C) 2006 WJG出版社。版权所有。
AIM: To study the anti-tumor effect of caffeic acid phenethyl ester (CAPE) and the influence of CAPE on beta-catenin associated signaling pathway in SW480 colorectal cancer (CRC) cells.METHODS: SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay. Cell cycle and cell apoptosis were analyzed using flow cytometry (FCM). Western blotting assay was used to evaluate the protein level of beta-catenin, c-myc and cyclinD1. beta-catenin localization was determined by indirect immunofluorescence.RESULTS: CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of GO /G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed beta-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of beta-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane.CONCLUSION: CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased beta-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE. (C) 2006 The WJG Press. All rights reserved.