β-肾上腺素能受体激活促进头颈癌生长转移及干预措施的进展研究
The Role of β-Adrenergic Signaling in Head and Neck Cancer Progression and Emerging Therapeutic Strategies
DOI: 10.12677/acm.2026.161340, PDF,   
作者: 袁 泽, 向 静, 李 勇*：重庆医科大学附属口腔医院，口腔疾病与生物医学重庆市重点实验室，重庆市高校市级口腔生物医学工程重点实验室，重庆
关键词: 慢性应激；β-肾上腺素能受体；头颈癌；肿瘤微环境；Chronic Stress； β-Adrenergic Receptor； Head and Neck Cancer； Tumor Microenvironment
摘要: 头颈部鳞状细胞癌(HNSCC)主要起源于黏膜鳞状上皮，高侵袭性威胁患者生存质量，慢性应激作为潜在诱因受到重视。因机体产生的高水平的肾上腺素(Epinephrine, E)与去甲肾上腺素(Norepinephrine, NE)可通过激活β-肾上腺素能受体(β-AR)从而调控肿瘤生物学行为。β-AR在肿瘤组织中表达显著升高，其中β2-AR高表达与肿瘤分化程度低、淋巴结转移率高及不良预后等密切相关，激活β-AR后能通过促进癌症干细胞样表型、上皮–间充质转化及重塑肿瘤微环境中多种信号分子等途径促进肿瘤进展。另一方面，多项研究表明β2-AR拮抗剂如普萘洛尔(Propranolol)，可通过抑制血管生成、减轻化疗耐药、降低肿瘤发生率等发挥抗肿瘤作用，其与MAPK抑制剂、EGFR拮抗剂、COX-2拮抗剂等联合使用时能增强抑癌作用。本文主要研究β-肾上腺素能通路激活对HNSCCs进展的影响，并为长期处于慢性应激压力下的患者开发高选择性靶向制剂及多模式联合治疗，为头颈癌治疗提供新策略。
Abstract: Head and neck squamous cell carcinoma (HNSCC), which primarily originates from the mucosal squamous epithelium, poses a significant threat to patient survival and quality of life due to its highly aggressive nature. Chronic stress has gained attention as a potential contributing factor. This is because elevated levels of epinephrine (E) and norepinephrine (NE) produced by the body can activate β-adrenergic receptors (β-ARs), thereby modulating tumor biological behavior. β-AR expression is significantly upregulated in tumor tissues. Notably, high expression of β2-AR strongly correlates with poor tumor differentiation, high rates of lymph node metastasis, and unfavorable prognosis. Upon activation, β-ARs promote tumor progression through various mechanisms, including fostering a cancer stem cell-like phenotype, inducing epithelial-mesenchymal transition (EMT), and remodeling the tumor microenvironment by modulating multiple signaling molecules. On the other hand, numerous studies have shown that β2-AR antagonists, such as propranolol, can exert anti-tumor effects by inhibiting angiogenesis, alleviating chemotherapy resistance, and reducing tumor incidence. Their combination with other agents, including MAPK inhibitors, EGFR antagonists, and COX-2 inhibitors, has been demonstrated to enhance the anti-cancer efficacy. This review focuses on the impact of β-adrenergic pathway activation on HNSCC progression. It aims to explore the development of highly selective targeted agents and multimodal combination therapies for patients under chronic stress, thereby providing novel strategies for the treatment of head and neck cancer.
文章引用：袁泽, 向静, 李勇. β-肾上腺素能受体激活促进头颈癌生长转移及干预措施的进展研究[J]. 临床医学进展, 2026, 16(1): 2787-2800. https://doi.org/10.12677/acm.2026.161340

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