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
alpha-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 microM
NS-398 and was significantly strong in 100 microM
NS-398. All cell lines exhibited apoptosis, which was identified by 4'-6-diamidino-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.