Conclusion
This study showed that β2-AR is related to a more advanced clinical stage and preoperative lymphatic metastasis. Additionally, a β2-AR blocker has a significant suppressive effect in OSCC.
Methods
Samples of 15 normal oral mucosal epithelial tissues, 60 surgically resected OSCC tissues, and 60 adjacent para-carcinoma tissues were collected. The expression of β1-adrenergic receptor and β2-AR was detected by real-time quantitative polymerase chain reaction and the Western blot test. SCC9 and Cal27 cell lines and primary OSCC cells also were included and treated with ICI-118,551 (MedChemExpress, Monmouth Junction, NJ), a selective β2-AR blocker. In addition, the Cal27 cell line was treated with propranolol (a nonselective β-adrenergic receptor blocker) to verify the suppressive effect of β2-AR blockade. For in vivo assays, Cal27 cells were subcutaneously injected in the tongue flank of nude mice. ICI-118,551 was orally administered to the mice in the treatment group daily. High-throughput sequencing was used to screen for changes in gene expression.
Purpose
The purpose of this project was to investigate the expression of β-adrenergic receptors in oral squamous cell carcinoma (OSCC) and the tumor suppressive activity of β2-adrenergic receptor (β2-AR) blockade. Materials and
Results
Real-time quantitative polymerase chain reaction and the Western blot test both showed that β1-adrenergic receptor and β2-AR were overexpressed in OSCC tissues and cells. A relationship was found between β2-AR and a more advanced clinical stage, as well as preoperative lymphatic metastasis. After treatment with ICI-118,551 or propranolol, the capacities for proliferation, invasion, and metastasis of OSCC cells were significantly inhibited. Tumor size was significantly different between the ICI-118,551 and control groups. The survival time in the ICI-118,551 group also was prolonged significantly. Moreover, high-throughput sequencing identified 19 affected signaling pathways, including mitogen-activated protein kinase and PI3K-Akt. We confirmed a significant change to the expression of several genes closely related to the progression of cancer.