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The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB-
Ezequiel Mariano Rivero1, Cecilia Pérez Piñero1, Lucía Gargiulo1
1Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires. Argentina.
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.
Insights
The beta-2 agonist salbutamol may help treat metastatic breast cancer by inhibiting tumor cell migration, invasion, and metastasis. This finding suggests salbutamol could be a valuable adjuvant therapy for patients with advanced breast cancer.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Breast cancer metastasis is a leading cause of cancer death in women.
- Adrenergic receptors are implicated in modulating the metastatic cascade, but their role in breast cancer is debated.
- Previous studies indicated beta-adrenergic agonists inhibit breast cancer cell proliferation and tumor growth.
Purpose of the Study:
- To investigate the effect of adrenergic agents on breast cancer cell migration, invasion, and metastasis.
- To evaluate the impact of salbutamol (a beta-2 agonist) and propranolol (a beta-blocker) on tumor progression parameters.
- To assess the expression of pro-metastatic genes and experimental metastasis in response to salbutamol.
Main Methods:
- Assessed cell migration using time-lapse videomicroscopy and modified Boyden chambers in IBH-6 and MDA-MB-231 cells.
- Evaluated invasion through Matrigel-coated Transwells and measured pro-metastatic gene expression via RT-qPCR.
- Studied experimental lung metastases in NSG mice following intravenous injection of cancer cells.
Main Results:
- Salbutamol and propranolol significantly reduced cell migration in both cell lines, while epinephrine increased it.
- Salbutamol inhibited invasion, enhanced extracellular matrix adhesion, and decreased pro-metastatic gene expression in MDA-MB-231 cells.
- Salbutamol treatment reduced the number and size of lung metastases in mice, though IBH-6 metastases were unaffected.
Conclusions:
- Salbutamol demonstrates potential as an adjuvant therapy for metastatic breast cancer.
- The findings support targeting beta-adrenergic pathways to combat breast cancer progression.
- Further research is warranted to explore salbutamol's efficacy and mechanisms in clinical settings.
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