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
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.