Huang Zeliu, Huang Laifeng, Zhang Chong, Chen Guosheng, Mai Huaming
Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Nanning, Guangxi, China; Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, Nanning, Guangxi, China; Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, Guangxi, China.
Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Nanning, Guangxi, China; Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, Nanning, Guangxi, China; Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, Guangxi, China.
Int Dent J. 2025 Apr;75(2):807-816. doi: 10.1016/j.identj.2024.06.014. Epub 2024 Jul 22.
β2-adrenergic receptor (β2-AR) and cyclooxygenase-2 (COX-2) are overexpressed in various malignant tumours including oral squamous cell carcinoma (OSCC), suggesting that they may contribute to the development of OSCC. This study aims to investigate the potential synergistic effect of β2-AR blockade and COX-2 inhibition on suppressing the development of OSCC.
Effects of blocking β2-AR and inhibiting COX-2 on migration and invasion of OSCC cells were detected by wound-healing assay and transwell invasion assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of genes related to the progression of OSCC. In vivo, OSCC xenograft models were established to evaluate the effect of combined treatment on survival time, tumour size, and submandibular lymph node metastasis. Immunohistochemistry, Western blot, and ELISA were used to detect the expression of invasion and metastasis relative genes.
In vitro, blocking β2-AR or inhibiting COX-2 alone could suppress invasion and metastasis of OSCC cells, and suppression with combined treatment was more significant. Expression of genes related to invasion and metastasis, including EGFR, TGF-β1, IL-1β, MMP2, and VEGFA, were downregulated significantly, especially in the combined treatment group. In vivo, the combined treatment could significantly prolong survival time in tumour-bearing mice and inhibit the growth of tumours. Furthermore, submandibular lymph node metastasis was less in the combined treatment group, and expression of the abovementioned genes was also downregulated.
The combination of β2-AR blockade and COX-2 inhibition can significantly suppress the development of OSCC via downregulating EGFR, TGF-β1, IL-1β, MMP2, and VEGFA. Findings suggest that the combined use of a β2-AR blocker and a COX-2 inhibitor could be a promising adjuvant therapy in OSCC. Both drugs are commonly prescribed, and their safety and efficacy are well established. Their use in adjuvants in OSCC should therefore be promoted in clinical practice.
β2-肾上腺素能受体（β2-AR）和环氧化酶-2（COX-2）在包括口腔鳞状细胞癌（OSCC）在内的多种恶性肿瘤中过表达，提示它们可能促进OSCC的发生发展。本研究旨在探讨β2-AR阻断与COX-2抑制在抑制OSCC发生发展方面的潜在协同作用。
采用伤口愈合试验和Transwell侵袭试验检测阻断β2-AR和抑制COX-2对OSCC细胞迁移和侵袭的影响。采用蛋白质印迹法和酶联免疫吸附测定（ELISA）检测与OSCC进展相关基因的表达。在体内，建立OSCC异种移植模型，以评估联合治疗对生存时间、肿瘤大小和下颌下淋巴结转移的影响。采用免疫组织化学、蛋白质印迹法和ELISA检测侵袭和转移相关基因的表达。
在体外，单独阻断β2-AR或抑制COX-2均可抑制OSCC细胞的侵袭和转移，联合治疗的抑制作用更显著。与侵袭和转移相关的基因，包括表皮生长因子受体（EGFR）、转化生长因子-β1（TGF-β1）、白细胞介素-1β（IL-1β）、基质金属蛋白酶2（MMP2）和血管内皮生长因子A（VEGFA）的表达均显著下调，尤其是在联合治疗组。在体内，联合治疗可显著延长荷瘤小鼠的生存时间并抑制肿瘤生长。此外，联合治疗组下颌下淋巴结转移较少，上述基因的表达也下调。
β2-AR阻断与COX-2抑制联合应用可通过下调EGFR、TGF-β1、IL-1β、MMP2和VEGFA显著抑制OSCC的发生发展。研究结果表明，联合使用β2-AR阻滞剂和COX-2抑制剂可能是一种有前景的OSCC辅助治疗方法。这两种药物均为常用处方药，其安全性和有效性已得到充分证实。因此，应在临床实践中推广它们在OSCC辅助治疗中的应用。
