2. Academic Validation
  3. Overexpression of β-Adrenergic Receptors and the Suppressive Effect of β2-Adrenergic Receptor Blockade in Oral Squamous Cell Carcinoma

Overexpression of β-Adrenergic Receptors and the Suppressive Effect of β2-Adrenergic Receptor Blockade in Oral Squamous Cell Carcinoma

  • J Oral Maxillofac Surg. 2020 Oct;78(10):1871.e1-1871.e23. doi: 10.1016/j.joms.2020.05.031.
Chong Zhang 1,  Xianxiang Liao 1,  Zhen Ma 1,  Shiqi Liu 1,  Fang Fang 1,  Huaming Mai 2
Affiliations

Affiliations

  • 1 Resident, Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Guangxi Medical University; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction; Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment; and Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, China.
  • 2 Professor, Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Guangxi Medical University; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction; Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment; and Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, China. Electronic address: huamingmai@163.com.
PMID: 32640209 DOI: 10.1016/j.joms.2020.05.031
Abstract

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 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.

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.

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.

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