| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Preclinical Pharmacology |
Departments of Internal Medicine [S. H. B., Y. M. P., B. S. K.], Pathology [E. S. J., B. K. K.], and General Surgery [D. K. K.], and WHO Collaborating Center for Reference and Research on Viral Hepatitis, College of Medicine, Catholic University of Korea, and Department of Biochemistry, College of Science, Yonsei University, Seoul, Korea [W. S. R.]
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 
-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 µM NS-398 and was significantly strong in 100 µM 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.
Commentary
Clin. Cancer Res. 2001 7: 1110.
This article has been cited by other articles:
|
|
 |
|
  S. Donnini, F. Finetti, R. Solito, E. Terzuoli, A. Sacchetti, L. Morbidelli, P. Patrignani, and M. Ziche EP2 prostanoid receptor promotes squamous cell carcinoma growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways FASEB J, August 1, 2007; 21(10): 2418 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xu, C. Han, K. Lim, and T. Wu Cross-talk between Peroxisome Proliferator-Activated Receptor {delta} and Cytosolic Phospholipase A2{alpha}/Cyclooxygenase-2/Prostaglandin E2 Signaling Pathways in Human Hepatocellular Carcinoma Cells Cancer Res., December 15, 2006; 66(24): 11859 - 11868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Davies, B. Knight, Y. W. Tian, G. C.T. Yeoh, and J. K. Olynyk Hepatic oval cell response to the choline-deficient, ethionine supplemented model of murine liver injury is attenuated by the administration of a cyclo-oxygenase 2 inhibitor Carcinogenesis, August 1, 2006; 27(8): 1607 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yan, J. Li, W. Ouyang, Q. Ma, Y. Hu, D. Zhang, J. Ding, Q. Qu, K. Subbaramaiah, and C. Huang NFAT3 is specifically required for TNF-{alpha}-induced cyclooxygenase-2 (COX-2) expression and transformation of Cl41 cells J. Cell Sci., July 15, 2006; 119(14): 2985 - 2994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Ralstin, E. A. Gage, M. T. Yip-Schneider, P. J. Klein, E. A. Wiebke, and C. M. Schmidt Parthenolide Cooperates with NS398 to Inhibit Growth of Human Hepatocellular Carcinoma Cells through Effects on Apoptosis and G0-G1 Cell Cycle Arrest Mol. Cancer Res., June 1, 2006; 4(6): 387 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Byun, M. A. Lee, S. Y. Roh, B. Y. Shim, S. H. Hong, Y. H. Ko, S. J. Ko, I. S. Woo, J. H. Kang, Y. S. Hong, et al. Association between Cyclooxygenase-2 and Matrix Metalloproteinase-2 Expression in Non-Small Cell Lung Cancer Jpn. J. Clin. Oncol., May 1, 2006; 36(5): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Cui, C.-H. Yu, and K.-Q. Hu In vitro and In vivo Effects and Mechanisms of Celecoxib-Induced Growth Inhibition of Human Hepatocellular Carcinoma Cells Clin. Cancer Res., November 15, 2005; 11(22): 8213 - 8221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Thomas and J. L. Abbruzzese Opportunities for Targeted Therapies in Hepatocellular Carcinoma J. Clin. Oncol., November 1, 2005; 23(31): 8093 - 8108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Waris and A. Siddiqui Hepatitis C Virus Stimulates the Expression of Cyclooxygenase-2 via Oxidative Stress: Role of Prostaglandin E2 in RNA Replication J. Virol., August 1, 2005; 79(15): 9725 - 9734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Malka, V. Pacault, T. De Baere, M. Ducreux, and V. Boige Antitumoral Effect of Celecoxib in Hepatocellular Carcinoma J. Clin. Oncol., July 20, 2005; 23(21): 4805 - 4806. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mollace, C. Muscoli, E. Masini, S. Cuzzocrea, and D. Salvemini Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors Pharmacol. Rev., June 1, 2005; 57(2): 217 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mayoral, A. Fernandez-Martinez, L. Bosca, and P. Martin-Sanz Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells Carcinogenesis, April 1, 2005; 26(4): 753 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Kern, M. M. Schoneweiss, D. Sahi, M. Bahlo, A. M. Haugg, H. U. Kasper, H. P. Dienes, H. Kaferstein, K. Breuhahn, and P. Schirmacher Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice Carcinogenesis, July 1, 2004; 25(7): 1193 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. WARNER and J. A. MITCHELL Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic FASEB J, May 1, 2004; 18(7): 790 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vecchini, V. Ceccarelli, F. Susta, P. Caligiana, P. Orvietani, L. Binaglia, G. Nocentini, C. Riccardi, G. Calviello, P. Palozza, et al. Dietary {alpha}-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells J. Lipid Res., February 1, 2004; 45(2): 308 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Choy and L. Milas Enhancing Radiotherapy With Cyclooxygenase-2 Enzyme Inhibitors: A Rational Advance? J Natl Cancer Inst, October 1, 2003; 95(19): 1440 - 1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Miyata, S. Koga, S. Kanda, M. Nishikido, T. Hayashi, and H. Kanetake Expression of Cyclooxygenase-2 in Renal Cell Carcinoma: Correlation with Tumor Cell Proliferation, Apoptosis, Angiogenesis, Expression of Matrix Metalloproteinase-2, and Survival Clin. Cancer Res., May 1, 2003; 9(5): 1741 - 1749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Minter, J. W. Eveson, S. Huntley, D. J. E. Elder, and A. Hague The Cyclooxygenase 2-selective Inhibitor NS398 Inhibits Proliferation of Oral Carcinoma Cell Lines by Mechanisms Dependent and Independent of Reduced Prostaglandin E2 Synthesis Clin. Cancer Res., May 1, 2003; 9(5): 1885 - 1897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Murakami, D. Takahashi, T. Kinoshita, K. Koshimizu, H. W. Kim, A. Yoshihiro, Y. Nakamura, S. Jiwajinda, J. Terao, and H. Ohigashi Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the {alpha},{beta}-unsaturated carbonyl group is a prerequisite Carcinogenesis, May 1, 2002; 23(5): 795 - 802. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
