Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Cyclooxygenase (COX) enzymes, particularly the inducible COX-2, play a significant role in carcinogenesis.
• Prostaglandins (PG), synthesized by COX enzymes, are implicated in cancer development.
• Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer where COX-2's role warrants investigation.

Purpose of the Study:

• To determine if COX-2 is overexpressed in HNSCC.
• To investigate whether retinoids inhibit epidermal growth factor (EGF)-mediated COX-2 activation.
• To explore the potential of retinoids and COX-2 inhibitors in HNSCC chemoprevention.

Main Methods:

• Quantitative analysis of COX-2 mRNA levels in HNSCC and normal oral mucosa samples.
• Immunoblot analysis to detect COX-2 protein expression in HNSCC tissues.
• In vitro studies using cultured oral squamous carcinoma cells to assess the effects of EGF and retinoids on COX-2 expression and PG synthesis.

Main Results:

• A nearly 100-fold increase in COX-2 mRNA was observed in HNSCC compared to normal mucosa.
• COX-2 protein was detected in a majority of HNSCC cases but not in normal mucosa.
• Retinoids effectively suppressed EGF-induced increases in COX-2 mRNA, COX-2 protein, and PG synthesis in cultured cells.

Conclusions:

• COX-2 is significantly overexpressed in HNSCC, indicating its potential involvement in the disease.
• Retinoids demonstrate chemopreventive potential by inhibiting COX-2 expression and activity.
• Combining retinoids with selective COX-2 inhibitors may offer a promising strategy for preventing and treating upper aerodigestive tract cancers.