Expression of Cyclooxygenase-2 (COX-2) in Hepatocellular Carcinoma and Growth Inhibition of Hepatoma Cell Lines by a COX-2 Inhibitor, NS-398

Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. In hepatocellular carcinoma (HCC), the expression pattern of COX-2 protein has been well correlated with the differentiation grade, suggesting that abnormal COX-2 expression plays an important role in hepatocarcinogene...

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Bibliographic Details
Published in:Clinical cancer research 2001-05, Vol.7 (5), p.1410-1418
Main Authors: Bae, S H, Jung, E S, Park, Y M, Kim, B S, Kim, B K, Kim, D G, Ryu, W S
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic agents
Antineoplastic Agents - pharmacology
Apoptosis
Biological and medical sciences
Carcinoma, Hepatocellular - enzymology
Carcinoma, Hepatocellular - pathology
Cell Division - drug effects
Chemotherapy
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - biosynthesis
Liver - enzymology
Liver Neoplasms - enzymology
Liver Neoplasms - pathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Membrane Proteins
Middle Aged
Neoplasm Staging
Nitrobenzenes - pharmacology
Pharmacology. Drug treatments
Prostaglandin-Endoperoxide Synthases - biosynthesis
Sulfonamides - pharmacology
Tumor Cells, Cultured
Tumors
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Summary:Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. In hepatocellular carcinoma (HCC), the expression pattern of COX-2 protein has been well correlated with the differentiation grade, suggesting that abnormal COX-2 expression plays an important role in hepatocarcinogenesis. We investigated the expression pattern and clinical significance of COX-2 in HCC tissues. In addition, we evaluated the efficacy of a selective COX-2 inhibitor, NS-398, in three hepatoma cell lines. Thirty-six HCC tissues, 15 hepatoma cell lines, 1 colorectal cell line (HT-29), and 1 fibroblast cell line (SV80) were included in the study. We evaluated serological tests and histological and radiological evaluations of HCC tissues. Immunohistochemical staining for COX-2 was performed on 36 HCC tissues and 17 cancer cell lines. A cell viability assay for growth inhibition of NS-398 in five cell lines was performed. Immunohistochemically, all six well-differentiated HCCs were positive, whereas 83% (10 of 12) of the poorly differentiated HCCs were negative. There was no significant relationship between the intensity of COX-2 expression and the level of α-fetoprotein, tumor size, presence of portal vein thrombosis, tumor capsule and metastasis, Tumor-Node-Metastasis staging, and growth types ( P > 0.05). According to the cell viability assay, NS-398 suppressed the growth of all cell lines, independent of the degree of COX-2 expression. The inhibitory effect on each cell line was identified in 10 μ m NS-398 and was significantly strong in 100 μ m NS-398. All cell lines exhibited apoptosis, which was identified by 4′-6diamidino-2-phenylindole staining. In conclusion, COX-2 may be a determinant of the differentiation grade of HCC, and the inhibition of COX-2 can induce growth suppression of hepatoma cell lines via induction of apoptosis.
ISSN:1078-0432
1557-3265