State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Arch Oral Biol. 2020 May;113:104712. doi: 10.1016/j.archoralbio.2020.104712. Epub 2020 Mar 21.
Chronic stress hormone norepinephrine (NE) has been previously reported to play a role in the development of cancer, but the correlation between NE and oral squamous cell carcinoma (OSCC) progression is not well understood.
To address this, the expression of adrenergic receptors (ARs) in human OSCC cell lines and clinic OSCC samples was detected, and the role of NEin vivo and in vitro was further investigated.
It was found that β2-AR was the main AR of NE in OSCC. Stimulation of OSCC cells with NE significantly increased the OSCC proliferation and invasion, which was, however, blocked by β2-AR inhibitor. NE could induce the phosphorylation of extracellular regulated protein kinases (ERK) and cAMP-response element binding protein (CREB). Inhibition of ERK and CREB pathway abrogated NE-induced OSCC invasion and proliferation. NE could enhance cancer stem cells (CSCs)-like phenotype and up-regulate the expression of stemness marker. In tumor-bearing nude mice, it was found that consecutive administration of NE significantly promoted the tumor growth, while daily injection of β2-AR inhibitor blocked this phenomenon.
Those findings indicated a critical role of the chronic stress hormone NE in OSCC progression. Inhibition of β2-AR may serve as a potential therapeutic strategy for protecting OSCC patients from chronic stress related deleterious effect.
慢性应激激素去甲肾上腺素（NE）先前被报道在癌症的发展中起作用，但 NE 与口腔鳞状细胞癌（OSCC）进展之间的相关性尚不清楚。
为了解决这个问题，检测了人 OSCC 细胞系和临床 OSCC 样本中肾上腺素能受体（AR）的表达，并进一步研究了 NE 在体内和体外的作用。
发现β2-AR 是 OSCC 中 NE 的主要 AR。NE 刺激 OSCC 细胞显著增加了 OSCC 的增殖和侵袭，而这一过程被β2-AR 抑制剂阻断。NE 可诱导细胞外调节蛋白激酶（ERK）和 cAMP 反应元件结合蛋白（CREB）的磷酸化。抑制 ERK 和 CREB 通路可阻断 NE 诱导的 OSCC 侵袭和增殖。NE 可增强癌症干细胞（CSC）样表型并上调干性标志物的表达。在荷瘤裸鼠中，发现连续给予 NE 可显著促进肿瘤生长，而每天注射β2-AR 抑制剂可阻断这一现象。
这些发现表明慢性应激激素 NE 在 OSCC 进展中起着关键作用。抑制β2-AR 可能是保护 OSCC 患者免受慢性应激相关有害影响的潜在治疗策略。
