Prostaglandin E2 receptors and COX enzymes in human hepatocellular carcinoma: role in the regulation of cell growth.

The aim of this study was to investigate the expression of prostaglandin E(2) receptors (EP(1-4)), cyclooxygenase-1 (COX-1), and COX-2 in nontumor and tumor human liver tissues, and also to evaluate the antitumor activity of selective EP(1) receptor antagonist used alone or in combination with COX-1 and COX-2 selective inhibitors. Semiquantitative PCR analyses revealed that EP(1-4), COX-1, and COX-2 mRNA expression was detected in nearly all the tissue samples assayed, although with a high variability between nontumor and tumor tissues. In vitro EP(1) receptor antagonist inhibited anchorage-independent cell growth and reduced the viability of hepatocellular carcinoma (HCC) cells in a dose-dependent manner. Moreover, treatment with the combination of EP(1) receptor antagonist and COX inhibitors produced a significantly greater cell growth inhibition than the single agent alone. These findings suggest that the EP(1) receptor may represent an important target for HCC treatment, and in addition they could provide preclinical support for a combined chemotherapeutic approach with EP(1) antagonists and COX inhibitors in the treatment of liver cancer.