Zhang Chong, Liao Xianxiang, Ma Zhen, Liu Shiqi, Fang Fang, Mai Huaming
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.
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.
J Oral Maxillofac Surg. 2020 Oct;78(10):1871.e1-1871.e23. doi: 10.1016/j.joms.2020.05.031. Epub 2020 May 28.
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 β-adrenergic receptor (β-AR) blockade.
Samples of 15 normal oral mucosal epithelial tissues, 60 surgically resected OSCC tissues, and 60 adjacent para-carcinoma tissues were collected. The expression of β-adrenergic receptor and β-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 β-AR blocker. In addition, the Cal27 cell line was treated with propranolol (a nonselective β-adrenergic receptor blocker) to verify the suppressive effect of β-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.
Real-time quantitative polymerase chain reaction and the Western blot test both showed that β-adrenergic receptor and β-AR were overexpressed in OSCC tissues and cells. A relationship was found between β-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.
This study showed that β-AR is related to a more advanced clinical stage and preoperative lymphatic metastasis. Additionally, a β-AR blocker has a significant suppressive effect in OSCC.
本项目旨在研究β-肾上腺素能受体在口腔鳞状细胞癌（OSCC）中的表达情况以及β-肾上腺素能受体（β-AR）阻断的肿瘤抑制活性。
收集15例正常口腔黏膜上皮组织样本、60例手术切除的OSCC组织样本以及60例癌旁组织样本。通过实时定量聚合酶链反应和蛋白质印迹试验检测β-肾上腺素能受体和β-AR的表达。还纳入了SCC9和Cal27细胞系以及原发性OSCC细胞，并用选择性β-AR阻滞剂ICI-118,551（MedChemExpress，新泽西州蒙茅斯 Junction）进行处理。此外，用普萘洛尔（一种非选择性β-肾上腺素能受体阻滞剂）处理Cal27细胞系以验证β-AR阻断的抑制作用。对于体内试验，将Cal27细胞皮下注射到裸鼠的舌侧腹。治疗组小鼠每日口服ICI-118,551。采用高通量测序筛选基因表达的变化。
实时定量聚合酶链反应和蛋白质印迹试验均显示β-肾上腺素能受体和β-AR在OSCC组织和细胞中过表达。发现β-AR与更晚期的临床分期以及术前淋巴转移之间存在关联。用ICI-118,551或普萘洛尔处理后，OSCC细胞的增殖、侵袭和转移能力受到显著抑制。ICI-118,551组与对照组的肿瘤大小存在显著差异。ICI-118,551组的生存时间也显著延长。此外，高通量测序鉴定出19条受影响的信号通路，包括丝裂原活化蛋白激酶和PI3K-Akt。我们证实了几个与癌症进展密切相关的基因的表达发生了显著变化。
本研究表明β-AR与更晚期的临床分期和术前淋巴转移有关。此外，β-AR阻滞剂在OSCC中具有显著的抑制作用。
