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首页> 外文期刊>European Journal of Pharmacology: An International Journal >A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator secretion in the human colon cancer cell line, HT-29.
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A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator secretion in the human colon cancer cell line, HT-29.

机译:对人结肠癌细胞株HT-29中尿激酶型纤溶酶原激活物分泌的胆碱能调节的药理学分析。

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摘要

Urokinase-type plasminogen activator (uPA) is an important factor for tumour cell invasion and metastasis. We recently showed that acetylcholine is an autocrine/paracrine growth factor for the human colon cancer cell line, HT-29, in part via the alpha7 subtype of the nicotinic acetylcholine receptors. In the current study, we investigated whether acetylcholine participates in the regulation of the protein expressions of also uPA and its receptor (uPAR) in the HT-29 cell line. Such were investigated by immunocytochemistry and Western blotting, and quantitation of uPA secretion was undertaken by ELISA. Stimulation of the cells for 24h with nicotine caused increased uPA secretion with peak effect (78% above the control) occurring at a nicotine concentration of 10nM. This effect was markedly inhibited by alpha-Bungarotoxin, thus showing the involvement of alpha7 nicotinic acetylcholine receptors. Basal uPA secretion was found to be partly dependent on ongoing activation of nicotinic receptors, suggesting tonic production of acetylcholine. Conversely, there was no cholinergic influence on the expression of uPAR. The current findings demonstrate novel aspects of receptor-mediated regulation of tumour metastatic potential via uPA secretion. This may suggest future pharmaceutical strategies in treatment of colorectal cancer.
机译:尿激酶型纤溶酶原激活剂(uPA)是肿瘤细胞侵袭和转移的重要因素。我们最近显示,乙酰胆碱是人结肠癌细胞系HT-29的自分泌/旁分泌生长因子,部分是通过烟碱乙酰胆碱受体的alpha7亚型引起的。在当前的研究中,我们研究了乙酰胆碱是否参与HT-29细胞系中uPA及其受体(uPAR)蛋白质表达的调节。通过免疫细胞化学和蛋白质印迹研究了这些,并且通过ELISA进行uPA分泌的定量。尼古丁刺激细胞24h导致uPA分泌增加,在尼古丁浓度为10nM时出现峰值效应(比对照高78%)。这种作用被α-真菌毒素显着抑制,因此显示出α7烟碱乙酰胆碱受体的参与。发现基础uPA分泌部分取决于烟碱样受体的持续活化,提示补品会产生乙酰胆碱。相反,对uPAR的表达没有胆碱能的影响。目前的发现证明了经由uPA分泌的受体介导的肿瘤转移潜能调节的新方面。这可能暗示了未来治疗结直肠癌的药物策略。

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