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

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 4(2): 199-206.

Author(s): Jidong Cheng and Toshikazu Hada.

Affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Mukogawacho 1-1, Nishinomiya, Hyogo 663, Japan.

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 Number: 2
First Page: 199
Last Page: 206
Page Count: 8
DOI: 10.2174/1568014053507122
Price: $58
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