Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line
Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line
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DOI：
10.1593/neo.06673
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Bhujwalla, Zaver M.
中科院分区：
文献类型：
--
作者：
Ackerstaff, Ellen;Gimi, Barjor;Bhujwalla, Zaver M.
实体瘤中存在的缺氧和酸性细胞外pH等不利的生理环境可能通过炎症反应和类花生酸的形成促进侵袭和转移。在这里，我们研究了抗炎剂吲哚美辛对人乳腺癌细胞系MDAMB-435在Dulbecco改良的老鹰（DME）为基础的或罗斯威尔公园纪念研究所（RPMI）为基础的细胞培养基中的侵袭和代谢的影响，使用磁共振兼容的侵袭测定。吲哚美辛治疗显着降低MDA-MB-435细胞的侵袭独立的培养和灌注条件下检查。细胞内胆碱磷脂代谢物的水平和甘油三酯（TG）浓度的这些细胞中检测到显着的变化，这取决于吲哚美辛治疗和基础细胞培养基。此外，乳腺癌细胞的遗传分析，生长和低剂量吲哚美辛在细胞培养中使用基于RPMI的培养基处理，揭示了上调的几个基因牵连环加氧酶非依赖性目标的吲哚美辛。这些数据证实了抗炎剂减少乳腺癌侵袭的能力，并证明，取决于细胞培养和灌注条件，吲哚美辛诱导的侵袭减少与胆碱磷脂代谢、TG代谢和基因表达的变化相关。
Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the anti-inflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME)-based or Roswell Park Memorial Institute (RPMI)-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG) concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenase-independent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.