摘要
背景:乳腺癌是世界上诊断最多的妇女,也是导致妇女癌症死亡的主要原因。转移是死亡的主要原因。涉及多个步骤的转移级联已经描述了肾上腺素能受体可以在多个水平上调节这一过程。然而,β-肾上腺素能作用在乳腺癌中是有争议的。我们先前已经表明,β- adrenergIC受体激动剂抑制细胞增殖和众多的乳腺癌模型中肿瘤的生长。 目的:本研究的目的是评估肾上腺素能效应在肿瘤进展相关的参数(迁移、浸润和转移)两人乳腺癌细胞里NES。方法:迁移评估IBH-6和时移电视MDA-MB-231细胞和改良的Boyden小室。通过涂层基底膜表达Transwells评估入侵促转移基因的RT-qPCR检测。实验性肿瘤转移研究在NSG免疫缺陷小鼠尾静脉注射的细胞进行。 结果:在这两个细胞系,沙丁胺醇(ββ2-受体激动剂)和普萘洛尔(β阻滞剂)显著降低细胞的迁移而肾上腺素产生相反的效果。此外,沙丁胺醇抑制侵袭对乳腺癌细胞株融合和增强细胞外基质的黏附。沙丁胺醇治疗也能降低MDA-MB-231细胞的促转移基因的表达。最后,这种化合物的数量显著减少,实验性肺转移MDA-MB-231 NSG免疫缺陷小鼠的大小。观察到IBH-6转移的形成没有影响。 结论:沙丁胺醇是治疗转移性乳腺癌的有效辅助药物。
关键词: 乳腺癌,转移,β-肾上腺素受体、沙丁胺醇、MDA-MB-231,IBH-6。
图形摘要
Current Cancer Drug Targets
Title:The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line
Volume: 17 Issue: 8
关键词: 乳腺癌,转移,β-肾上腺素受体、沙丁胺醇、MDA-MB-231,IBH-6。
摘要: Background: Breast cancer is the most diagnosed and the major cause of cancer death in women worldwide. Metastasis is the main cause of these deaths. The metastatic cascade involves multiple steps and it has been described that adrenergic receptors can modulate this process at multiple levels. However, β -adrenergic action in breast cancer is controversial. We have previously shown that β-adrenergic agonists inhibit cell proliferation and tumor growth of numerous breast cancer models.
Objective: The purpose of the present investigation was to evaluate adrenergic effect in parameters related to tumor progression (migration, invasion and metastases) in two human breast cancer cell lines. Methods: Migration was assessed in IBH-6 and MDA-MB-231 cells by time-lapse videomicroscopy and modified Boyden chambers. Invasion was evaluated by Transwells coated with Matrigel and expression of pro-metastatic genes was determined by RT-qPCR. Experimental metastases studies were performed by injection of the cells in the tail vein of NSG immuno-deficient mice.
Results: In both cell lines, salbutamol (β2-agonist) and propranolol (β-blocker) significantly diminished cell migration while epinephrine exerted opposite effects. Moreover, salbutamol inhibited invasion of both breast cancer cell lines and enhanced adhesion to extracellular matrix. Salbutamol treatment was also able to decrease the expression of pro-metastatic genes in MDA-MB-231 cells. Finally, this compound decreased the number and size of MDA-MB-231 lung experimental metastases in NSG immuno- deficient mice. No effect on the establishment of IBH-6 metastases was observed.
Conclusion: Our results suggest that salbutamol could be an effective adjuvant drug for the treatment of metastatic breast cancer.
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The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line, Current Cancer Drug Targets 2017; 17 (8) . https://dx.doi.org/10.2174/1568009617666170330151415
DOI https://dx.doi.org/10.2174/1568009617666170330151415 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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