6533b7d8fe1ef96bd126af69

RESEARCH PRODUCT

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

Antonina AzzolinaGiuseppe MontaltoDaniela FoderàAntonella CusimanoMelchiorre CervelloNatale D'alessandroMonica NotarbartoloNadia LampiasiLydia Giannitrapani

subject

Malemedicine.medical_specialtyEP receptorSettore MED/09 - Medicina InternaCarcinoma Hepatocellularmedicine.drug_classProstaglandinmedicine.medical_treatmentGeneral Biochemistry Genetics and Molecular Biologyhepatocellular carcinoma (HCC)History and Philosophy of ScienceInternal medicineCell Line Tumormedicinecell growthHumansReceptors Prostaglandin EProstaglandin E2ReceptorAgedCOX-1ChemistryCell growthGeneral NeuroscienceLiver NeoplasmsCOX-2Middle Agedmedicine.diseaseReceptor antagonistNSAIDIn vitroCyclooxygenaseEndocrinologyProstaglandin-Endoperoxide SynthasesHepatocellular carcinomaSettore BIO/14 - FarmacologiaCancer researchFemaleLiver cancerCell DivisionProstaglandin Emedicine.drug

description

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.

http://hdl.handle.net/10447/37533