Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.
Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.
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DOI：
10.1371/journal.pone.0061836
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Morin PJ
中科院分区：
文献类型：
--
作者：
Valle BL;D'Souza T;Becker KG;Wood WH 3rd;Zhang Y;Wersto RP;Morin PJ
流行病学研究表明，经常使用非甾体抗炎药（NSAID）与降低各种癌症的风险有关。此外，在体外和小鼠模型中的实验已经证明，NSAID减少了几种癌症的肿瘤发生和/或进展。然而，有有限的临床前研究调查NSAID在卵巢癌中的作用。在这里，我们研究了两种非甾体抗炎药，双氯芬酸和吲哚美辛，在卵巢癌细胞系和异种移植小鼠模型的影响。双氯芬酸和吲哚美辛处理通过诱导细胞周期停滞和凋亡来降低细胞生长。此外，在卵巢癌异种移植模型中，双氯芬酸和吲哚美辛可缩小肿瘤体积。为了确定可能的分子途径介导的作用，非甾体抗炎药治疗卵巢癌，我们进行了微阵列分析卵巢癌细胞与吲哚美辛或双氯芬酸。有趣的是，发现在双氯芬酸或吲哚美辛治疗后下调的几个基因是E2 F1的转录靶基因。在用双氯芬酸和吲哚美辛处理后，E2 F1在mRNA和蛋白水平下调，并且E2 F1的过表达从双氯芬酸和吲哚美辛的生长抑制作用中拯救细胞。总之，NSAID双氯芬酸和吲哚美辛在体外和体内卵巢癌中发挥抗增殖作用，NSAID的作用可能部分通过下调E2 F1介导。
Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs) drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.
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影响因子：
7.3
作者：
Gorgoulis, VG;Zacharatos, P;Papavassiliou, AG
通讯作者：
Papavassiliou, AG
影响因子：
11.5
作者：
Cui, W;Yu, CH;Hu, KQ
通讯作者：
Hu, KQ
DOI：
10.1006/bbrc.2001.5819
发表时间：
2001-11-02
影响因子：
3.1
作者：
Adhami, VM;Afaq, F;Ahmad, N
通讯作者：
Ahmad, N
影响因子：
4.6
作者：
Bock, Jonathan M.;Menon, Sarita G.;Trask, Douglas K.
通讯作者：
Trask, Douglas K.
影响因子：
6.4
作者：
Chirasani, Sridhar R.;Leukel, Petra;Grauer, Oliver M.
通讯作者：
Grauer, Oliver M.