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Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer
1Anne Fisher Nutrition Center, Strang Cancer Prevention Center, New York, New York, USA.
Abstract:
Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX-2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX-2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)-mediated activation of COX-2 expression. Levels of COX-2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100-fold increase in amounts of COX-2 mRNA was detected in HNSCC. By immunoblot analysis, COX-2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF-mediated induction of COX-2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX-2 mRNA, COX-2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX-2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX-2 expression. Combining a retinoid with a selective COX-2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.
Insights
Cyclooxygenase-2 (COX-2) is overexpressed in head and neck squamous cell carcinoma. Retinoids suppress epidermal growth factor-induced COX-2 activation, suggesting a role in cancer chemoprevention.
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.