Beta adrenergic receptor activation inhibits oral cancer migration and invasiveness

• Published in: Archives of oral biology Vol. 118; p. 104865
• Main Authors: Bravo-Calderón, Diego Mauricio, Assao, Agnes, Garcia, Natália Galvão, Coutinho-Camillo, Cláudia Malheiros, Roffé, Martin, Germano, Janaína Naiara, Oliveira, Denise Tostes
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2020
• Subjects: Adrenergic beta-Antagonists - pharmacology; beta-adrenergic receptor; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Dentistry; Humans; Mouth Neoplasms - drug therapy; Mouth Neoplasms - pathology; Neoplasm Invasiveness; Oral cancer; Propranolol - pharmacology; Receptors, Adrenergic, beta - metabolism; stress; Oral cancer; stress; beta-adrenergic receptor
• ISSN: 0003-9969; 1879-1506
• DOI: 10.1016/j.archoralbio.2020.104865

•The oral squamous cell carcinoma cell lines (SCC-9 and SCC-25) showed lower β2-AR expression than that of the normal oral mucosa.•β2-AR activation by stress hormones such as norepinephrine can reduce the migration and invasion of oral squamous cell carcinoma cell lines.•The blockade by propranolol partially reversed the effect of norepinephrine on the invasiveness of oral cancer cell lines. The aim of this study was to verify β2-AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of this receptor in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR. Cell migration and invasion were analyzed by wound healing assay and transwell invasion camera system. Different concentrations (0.1, 1 and 10 μM) of norepinephrine were used to stimulate, and 1 μM propranolol was used to block the beta-adrenergic receptors on cancer cells. Differences in median values of SCC-9 and SCC-25 and β2-AR protein expression were analyzed by Friedman test and in case of significant differences; pairwise comparisons were performed using Bonferroni correction. The results showed that the β2-AR gene and protein expression were observed in both oral cancer cell lines. The concentration of 10 μM of norepinephrine significantly inhibited (p ≤ 0.05) migration of SCC-9 and SCC-25 cell lines. Furthermore, there was a significant reduction (p ≤ 0.05) in the effect of norepinephrine on cell migration when the β2-AR was inhibited by propranolol. The blockade by propranolol showed a tendency to reverse the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. The use of beta-adrenergic receptor agonists could become an adjuvant therapeutic target in the treatment of this malignancy.