Inhibition of Cyclooxygenase‐2 Expression: An Approach to Preventing Head and Neck Cancer

Abstract

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.