Combination of β2-AR Blocker and COX-2 Inhibitor Suppresses Development of Oral Squamous Cell Carcinoma

Abstract

Background To study the effect of inhibiting progression of oral squamous cell carcinoma (OSCC) through blocking β2-adrenergic receptor (β2-AR) and inhibiting Cyclooxygenase-2 (COX-2). Methods Transwell invasion assay and wound-healing assay were used to investigate whether invasion and metastasis of OSCC cells (SCC9, Cal27 cell lines and primary OSCC cells) would be inhibited after treated by β2-AR blocker (ICI118,551), COX-2 inhibitor (Etodolac) or both. Real time quantitative polymerase chain reaction (RT-qPCR), Western blot and enzyme linked immunosorbent assay (ELISA) were used to detect expression change of genes related to invasion and metastasis in OSCC cells after drug treatment. In vivo, 6-8 weeks old female Balb/c nude mice were randomly divided into control group, ICI118,551 treatment group, etodolac treatment group and combined treatment group. Cal27 cells were used to establish OSCC xenograft models. The survival days, tumor sizes and lymph nodes metastasis were compared among these groups. Immunohistochemistry, Western blot and ELISA were carried out to detect expression change of invasion and metastasis relative genes. Results ICI118,551 or etodolac could inhibit invasion and metastasis of OSCC cells, and the inhibition of combined treatment was more significant. Moreover, RT-qPCR and Western blot showed that epidermal growth factor receptor (EGFR), transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β), matrix metalloproteinase 2 (MMP2) were downregulated after treatment, especially in combined treatment group. In vivo, the combined treatment group could significantly prolong survival days and inhibit tumor size. Immunohistochemistry, Western blot and ELISA showed the expression of above-mentioned genes were also downregulated. Conclusions Invasion and metastasis of OSCC can be inhibited through blocking β2-AR and inhibiting COX-2, it can be a potential treatment of OSCC.