Norepinephrine induced epithelial-mesenchymal transition in HT-29 and A549 cells in vitro
Norepinephrine induced epithelial-mesenchymal transition in HT-29 and A549 cells in vitro
复制标题
去甲肾上腺素体外诱导 HT-29 和 A549 细胞上皮间质转化
DOI：
10.1007/s00432-015-2044-9
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发表时间：
2016-02-01
影响因子：
3.6
通讯作者：
Jiang, Yu
中科院分区：
文献类型：
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作者：
Zhang, Jie;Deng, Yao-tiao;Jiang, Yu
目的去甲肾上腺素(NE)参与癌细胞上皮-间充质转化(EMT)。然而，人们对其潜在机制知之甚少。方法用去甲肾上腺素(NE)、β-肾上腺素能受体(β-AR)拮抗剂(心得安)或转化生长因子-β(TGF-β)受体I型激酶抑制剂(Ly2157299)分别作用于HT-29和A549细胞。光镜、电子显微镜和免疫荧光染色观察细胞形态。细胞迁移实验和Matrigel侵袭实验分别检测细胞的迁移和侵袭能力。测定转化生长因子-β1和环磷酸腺苷(CAMP)含量。结果去甲肾上腺素刺激细胞分泌转化生长因子β1，促进细胞内cAMP合成，诱导细胞形态改变，增强细胞的迁移和侵袭能力。在NE处理的癌细胞中观察到EMT标志物的诱导。心得安或LY2157299可抑制NE的作用。β-AR/转化生长因子-β1信号通路/p-SMAD3/Snail和β-AR/转化生长因子-β1信号通路/缺氧诱导因子-1α/Snail是两条信号转导通路。结论转化生长因子-β1信号转导通路是去甲肾上腺素诱导癌细胞EMT的重要因素。数据还表明，心理压力可能是增强癌细胞迁移或侵袭能力的风险因素。
Purpose Norepinephrine (NE) has been implicated in epithelial-mesenchymal transition (EMT) of cancer cells. However, the underlying mechanism is poorly understood. The goal of this study was to explore the effect of NE on cancer cell EMT and to investigate the potential mechanism.Methods HT-29 and A549 cells were treated with NE, beta-adrenergic receptor (beta-AR) antagonist (propranolol) or inhibitor of transforming growth factor-beta (TGF-beta) receptor type I kinase (Ly2157299). Morphology of cells was observed with optical and electron microscope and immunofluorescence staining. Cellular migration and invasion were tested with transwell migration assay and Matrigel invasion assay, respectively. TGF-beta 1 and cyclic adenosine monophosphate (cAMP) were quantified. EMT markers and signaling pathway were measured by RT-PCR and western blot.Results NE stimulated TGF-beta 1 secretion and intracellular cAMP synthesis, induced morphological alterations in HT-29 and A549 cells, and enhanced their ability of migration and invasion. EMT markers induction was observed in NE-treated cancer cells. The effect of NE could be inhibited by propranolol or Ly2157299. beta-AR/TGF-beta 1 signaling/p-Smad3/Snail and beta-AR/TGF-beta 1 signaling/HIF-1 alpha/Snail were two signaling pathways.Conclusion These findings demonstrated that TGF-beta 1 signaling pathway was a significant factor of NE-induced cancer cells EMT. The data also suggested that psychological stress might be a risk factor which enhances the ability of migration or invasion of cancer cells.