Antiproliferative effects of COX-2 inhibitor celecoxib on human breast cancer cell lines
Antiproliferative effects of COX-2 inhibitor celecoxib on human breast cancer cell lines
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DOI：
10.1007/s11010-010-0682-4
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发表时间：
2011-04-01
影响因子：
4.3
通讯作者：
Miglietta, Antonella
中科院分区：
文献类型：
--
作者：
Bocca, Claudia;Bozzo, Francesca;Miglietta, Antonella
诱导型考克斯-2酶在人乳腺癌中过表达，其过表达通常与血管生成、细胞凋亡失调和预后不良相关。这一观察结果可以解释非甾体抗炎药和考克斯-2抑制剂对乳腺癌治疗的有益作用。在这里，我们评估了塞来昔布，一种选择性考克斯-2抑制剂，及其硝基氧衍生物对人乳腺癌细胞的抗增殖活性，其特点是低和高考克斯-2表达，分别。在ER α（+）MCF-7细胞中，塞来昔布及其衍生物可诱导强烈的细胞生长抑制作用，该抑制作用与ER α表达和活化减少相关。这些作用可能与ERK和Akt抑制以及PP 2A和PTEN诱导直接相关。在该细胞系中，药物仅对考克斯-2水平产生弱作用，而它们能够降低芳香化酶表达。相反，在ER α（-）MDA-MB-231细胞中，两种药物均诱导考克斯-2的显著抑制，该抑制与芳香酶表达和细胞增殖的减少有关。在这两种细胞系中，药物的作用均与细胞侵袭的抑制有关。
The inducible COX-2 enzyme is over-expressed in human breast cancer and its over-expression generally correlates with angiogenesis, deregulation of apoptosis and worse prognosis. This observation may explain the beneficial effect of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors on breast cancer treatment. Here, we evaluated the antiproliferative activity of celecoxib, a selective COX-2 inhibitor, and its nitro-oxy derivative on human breast cancer cells characterized by low and high COX-2 expression, respectively. In ER alpha(+) MCF-7 cells celecoxib and its derivative induce a strong inhibition of cell growth, inhibition that is associated with the reduction of ER alpha expression and activation. These effects may be directly associated with ERK and Akt suppression and with PP2A and PTEN induction. In this cell line the drugs exert only weak effect on COX-2 level while they are able to reduce aromatase expression. On the contrary, in ER alpha(-) MDA-MB-231 cells, both drugs induce a marked inhibition of COX-2, inhibition that is associated with the reduction of aromatase expression and of cell proliferation. In both cell lines the effects of the drugs are associated with the suppression of cell invasion.