The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line

Author(s): Ezequiel Mariano Rivero, Cecilia Pérez Piñero, Lucía Gargiulo, Frank Entschladen, Kurt Zänker, Ariana Bruzzone, Isabel Alicia Lüthy*.

Journal Name: Current Cancer Drug Targets

Volume 17 , Issue 8 , 2017

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Graphical Abstract:


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.

Keywords: Breast cancer, metastasis, β-adrenoceptors, salbutamol, MDA-MB-231, IBH-6.

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Article Details

Year: 2017
Page: [756 - 766]
Pages: 11
DOI: 10.2174/1568009617666170330151415
Price: $58

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