Abstract
Overexpression of cyclooxygenase-2 in oral cancer increases lymph node metastasis and is associated with a poor prognosis. The potential of celecoxib (CXB) use is reported in cancer treatment by inhibiting proliferation through apoptosis, but the effects on the epithelial-mesenchymal transition (EMT) and cancer cell mobility remain unclear. We performed a preclinical study and population-based study to evaluate CXB use in the prevention of oral cancer progression and occurrence. The in-vitro findings showed that CXB is involved in the inhibition of EMT and cell mobility through blocking transcription factors (Slug, Snail and ZEB1), cytoplasmic mediators (focal adhesion kinase (FAK), vimentin and β-catenin), cell adhesion molecules (cadherins and integrins), and surface receptors (AMFR and EGFR). The murine xenograft model showed a 65% inhibition in tumour growth after a 5-week treatment of CXB compared to placebo. Xenograft tumours in placebo-treated mice displayed a well-to-moderate/moderate differentiated SCC grade, while those from CXB-treated mice were well differentiated. The expression levels of membrane EGFR, and nuclear FAK, Slug and ZEB1 were decreased in the xenograft tumours of CXB-treated mice. A retrospective cohort study showed that increasing the daily dose and medication time of CXB was associated with oral cancer prevention. The findings provide an alternative prevention strategy for oral cancer development with CXB use.
Highlights
Oral squamous cell carcinoma (OSCC) is a head and neck cancer and a major cause of significant morbidity worldwide[1]
We observed that CXB inhibited OSCC cell proliferation in 24 h of treatment assessed by PCNA immunoblotting and Ki-67 immunocytochemistry and immunofluorescence (ICC-IF) assays (Fig. 1B and C)
Whether CXB use both decreases OSCC cell proliferation and inhibits cancer cell motility and epithelial-mesenchymal transition (EMT) programs through COX-2 inhibition is worthy of attention
Summary
Oral squamous cell carcinoma (OSCC) is a head and neck cancer and a major cause of significant morbidity worldwide[1]. Overexpression of COX-2 signalling is associated with lymph node metastasis in head and neck cancer patients[6]. A decreased epithelial E-cadherin level was found to be associated with increased PGE2 synthesis through prostaglandin EP2 receptors during SCC progression[17]. These findings indicate that abnormal COX-2/PGE2 overexpression is involved in cancer development, and whether it could be reversible by prescribing medication interventions of COX-2 inhibitors in OSCC patients remains to be investigated. We first attempt to determine the possible efficacy of CXB in inhibiting the OSCC cancer cell proliferation, mobility and EMT programs through several related signalling pathways using pre-clinical models. We perform a population-based study to evaluate the benefit of CXB use as an early chemopreventive strategy on the occurrence of OSCC development
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call