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

(EP1-4), cyclooxygenase-1 (COX-1), and COX-2 in nontumor and tumor human liver tissues, and also to evaluate the antitumor activity of selective EP1 receptor antagonist used alone or in combination with COX-1 and COX-2 selective inhibitors. Semiquantitative PCR analyses revealed that EP1-4, 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 EP1 receptor antagonist inhibited anchorageindependent cell growth and reduced the viability of hepatocellular carcinoma (HCC) cells in a dose-dependent manner. Moreover, treatment with the combination of EP1 receptor antagonist and COX inhibitors produced a significantly greater cell growth inhibition than the single agent alone. These findings suggest that the EP1 receptor may represent an important target for HCC treatment, and in addition they could provide preclinical support for a combined chemotherapeutic approach with EP1 antagonists and COX inhibitors in the treatment of liver cancer.