Department of Surgery, Stomatology, Pathology and Radiology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Brazil.
International Research Center, A.C.Camargo Cancer Center, São Paulo, SP, Brazil.
Arch Oral Biol. 2020 Oct;118:104865. doi: 10.1016/j.archoralbio.2020.104865. Epub 2020 Aug 7.
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.
本研究旨在验证口腔鳞状细胞癌细胞系（SCC-9 和 SCC-25）中β2-AR 的表达，并研究该受体在这些肿瘤细胞迁移和侵袭中的作用。
研究 SCC-9 和 SCC-25 细胞中β2-AR 的基因和蛋白表达。通过划痕愈合试验和 Transwell 侵袭相机系统分析细胞迁移和侵袭。使用不同浓度（0.1、1 和 10µM）去甲肾上腺素刺激，并使用 1µM 普萘洛尔阻断癌细胞上的β-肾上腺素能受体。使用 Friedman 检验分析 SCC-9 和 SCC-25 以及β2-AR 蛋白表达中位数的差异，在差异显著的情况下，使用 Bonferroni 校正进行两两比较。
结果表明，β2-AR 基因和蛋白表达均在两种口腔癌细胞系中观察到。10µM 去甲肾上腺素的浓度显著抑制（p≤0.05）SCC-9 和 SCC-25 细胞系的迁移。此外，当用普萘洛尔抑制β2-AR 时，去甲肾上腺素对细胞迁移的作用明显降低（p≤0.05）。普萘洛尔的阻断显示出逆转去甲肾上腺素对 SCC-9 和 SCC-25 侵袭作用的趋势。
β-肾上腺素能受体激动剂的使用可能成为治疗这种恶性肿瘤的辅助治疗靶点。
