Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Bahar Tunctan
Department of Pharmacology
Faculty of Pharmacy
Mersin University
Mersin, 33169
Turkey

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The Significance of COX-2 and COX-2 Inhibitors in Liver Fibrosis and Liver Cancer

Author(s): Jidong Cheng, Toshikazu Hada.

Abstract:

Hepatitis, liver cirrhosis and liver cancer are major liver diseases particularly in Asia. Liver cancer is also one of the leading cancers causing death in the world. Cyclooxygenase 2 (COX-2) is a highly inducible and key rate-limiting enzyme involved in the production of prostaglandins (PGs), prostacyclin, and thromboxanes. COX-2 is expressed in response to a variety of proinflammatory agents and cytokines. COX-2 is associated with liver pathogenesis, including fibrosis and cancer. It has been shown that COX-2 is up-regulated in cirrhotic tissues adjacent to hepatocellular carcinoma (HCC) and well-differentiated HCC. We and others also observed the up-regulation of COX-2 in liver fibrosis. The chemopreventive efficacy of COX-2 inhibitors in liver fibrosis and hepato-carcinogenesis has been observed in animal experimental models. COX-2 inhibitors have also exhibited significant anti-proliferative effects on HCC cell lines by inducing apoptosis and cell cycle arrest and blocking growth signaling pathways. These results raise the possibility that COX-2 may be a target for the prevention or treatment of liver fibrosis, hepato-carcinogenesis and liver cancer, as it is for colon cancer. In this article, we review recent studies on the role of COX-2 in liver fibrosis and liver cancer, and discuss rationale and feasibility of COX-2 inhibitors in chemoprevention and treatment of liver fibrosis and liver cancer.

Keywords: liver fibrosis, hepato-carcinogenesis, liver cancer, cyclooxygenase 2, cyclooxygenase 2 inhibitor

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Article Details

VOLUME: 4
ISSUE: 2
Year: 2005
Page: [199 - 206]
Pages: 8
DOI: 10.2174/1568014053507122
Price: $58