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Prostaglandin E 2 Receptors and COX Enzymes in Human Hepatocellular Carcinoma
Author(s) -
Cusimano Antonella,
Foderà Daniela,
Lampiasi Nadia,
Azzolina Antonina,
Notarbartolo Monica,
Giannitrapani Lydia,
D'Alessandro Natale,
Montalto Giuseppe,
Cervello Melchiorre
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.03701.x
Subject(s) - receptor , antagonist , hepatocellular carcinoma , receptor antagonist , prostaglandin e2 , prostaglandin , pharmacology , cancer research , cell growth , cyclooxygenase , medicine , chemistry , enzyme , biology , biochemistry
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.