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Blocking β2-AR and Inhibiting COX-2: A Promising Approach to Suppress OSCC Development
Zeliu Huang1, Laifeng Huang1, Chong Zhang1
1Department 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.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Blocking β2-adrenergic receptor (β2-AR) and cyclooxygenase-2 (COX-2) together significantly suppresses oral squamous cell carcinoma (OSCC) development by downregulating key genes. This combination therapy shows promise for treating OSCC.
Area of Science:
- Oncology
- Pharmacology
Background:
- β2-adrenergic receptor (β2-AR) and cyclooxygenase-2 (COX-2) are overexpressed in oral squamous cell carcinoma (OSCC).
- These molecules are implicated in the development and progression of OSCC.
Purpose of the Study:
- To investigate the synergistic effect of β2-AR blockade and COX-2 inhibition on OSCC suppression.
- To evaluate the impact of combined therapy on OSCC cell invasion, metastasis, and in vivo tumor growth.
Main Methods:
- In vitro assays (wound-healing, transwell invasion) and Western blot/ELISA were used to assess OSCC cell behavior and gene expression.
- In vivo OSCC xenograft models were established to evaluate survival, tumor size, and metastasis.
- Immunohistochemistry, Western blot, and ELISA were employed to analyze gene expression in vivo.
Main Results:
- Combined β2-AR blockade and COX-2 inhibition significantly suppressed OSCC cell invasion and metastasis in vitro.
- The combined treatment downregulated key genes including EGFR, TGF-β1, IL-1β, MMP2, and VEGFA.
- In vivo, combined therapy prolonged survival, inhibited tumor growth, reduced lymph node metastasis, and downregulated these genes.
Conclusions:
- Combination therapy of β2-AR blockade and COX-2 inhibition effectively suppresses OSCC development.
- This approach downregulates critical genes involved in invasion and metastasis (EGFR, TGF-β1, IL-1β, MMP2, VEGFA).
- Findings suggest this combination is a promising adjuvant therapy for OSCC, leveraging well-established drugs.
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