Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer
Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer
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DOI：
10.1016/j.jep.2015.02.015
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发表时间：
2015-05-13
影响因子：
5.4
通讯作者：
He, Lei
中科院分区：
文献类型：
--
作者：
Liu, Wei;Yi, Dan-Dan;He, Lei
民族药理学相关性：荷叶在中国最早的中医文献中被记载为“本草纲目”，是一种用于凝血、痢疾、头晕的草药。近年来，N.已经显示出，荷叶提取物具有几种药理学性质，包括抗病毒和抗癌。本研究的目的是探讨NF在尼古丁诱导的非小细胞肺癌（NSCLC）进展中的抗肿瘤作用的分子机制。材料与方法：采用肿瘤细胞增殖实验检测NF对尼古丁预处理或未预处理的人肺腺癌上皮细胞株A549增殖的影响。TOP-Flash报告基因分析用于研究NF和/或尼古丁存在下肿瘤细胞中Wnt/β-catenin信号传导的活性。使用FITC-Annexin V和PI检测试剂盒通过流式细胞术测量细胞凋亡。采用RT-PCR和Western blot方法分别检测mRNA和蛋白表达水平。在体内实验中，肿瘤样品固定在福尔马林和石蜡包埋的额外的分析，通过免疫组化和TUNEL staining.Results：NF显着抑制尼古丁的存在下，非小细胞肺癌细胞的增殖，抑制Wnt/β-catenin信号的活性，增强Axin的稳定性，并诱导凋亡。NF下调β-catenin及其下游靶基因c-myc、cyclin D和VEGF-A的表达水平。NF还可降低Bcl-2/Bax比值，这可能是NF具有促凋亡作用的原因之一。结论：NF对尼古丁诱导的非小细胞肺癌（NSCLC）具有明显的抑制作用，其机制可能与NF降低Wnt/beta-catenin信号通路的活性有关。因此，本文所述的工作强调了这种传统药物的重要性，并为NSCLC的预防和治疗提供了一种潜在的新型替代方案。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: The leaves of Nelumbo nucifera Gaertn are recorded in the earliest written documentation of traditional Chinese medicinal as "Ben Cao Gang Mu", a medicinal herb for blood clotting, dysentery and dizziness. Recently, nuciferine (NF), one of N. nucifera Gaertn leaf extracts has been shown to possess several pharmacological properties, including anti-viral and anti-cancer. The aim of this study is to investigate the underlying molecular mechanism of the anti-cancer activity of NF in NSCLC progression induced by nicotineMaterials and methods: The effect of NF on proliferation of A549 (human lung adenocarcinoma epithelial cell line) pretreated with or without nicotine was detected by tumor cell proliferation assay. TOP-Flash reporter assay was applied to investigate the activity of Wnt/beta-catenin signaling in tumor cells in the presence of NF and/or nicotine. Apoptosis was measured using a FITC-Annexin V and PI detection kit by flow cytometry. In addition, mRNA or protein expression levels were respectively tested by quantitative RT-PCR or western blot. In vivo experiments, tumor samples were fixed in formalin and embedded in paraffin for additional analyses by immunohistochemistry and TUNEL staining.Results: NF significantly inhibited the proliferation of NSCLC cells in the presence of nicotine, suppressed the activity of Wnt/beta-catenin signaling, enhanced the stabilization of Axin, and induced apoptosis. NF down-regulated the expression levels of beta-catenin and its downstream targets including c-myc, cyclin D and VEGF-A. NF also decreased the ratio of Bcl-2/Bax, which may explain the pro-apoptosis effect of NF. In tumor xenograft nude mice, NF not only inhibited the growth of non-small cell lung cancer (NSCLC) cells, but also remarkably alleviated the injury induced by nicotine in liver function.Conclusions: NF has the remarkable effect to inhibit nicotine-induced NSCLC progression, which was due to its ability to reduce the activity of Wnt/beta-catenin signaling. Thus, the work stated here emphasizes the importance of this traditional medicine and presents a potential novel alternative to NSCLC prevention and therapy. (C) 2015 Elsevier Ireland Ltd. All rights reserved.