Liver Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 28, 2007; 13(8): 1175-1181
Published online Feb 28, 2007. doi: 10.3748/wjg.v13.i8.1175
Selective COX-2 inhibitor, NS-398, suppresses cellular proliferation in human hepatocellular carcinoma cell lines via cell cycle arrest
Ji Yeon Baek, Wonhee Hur, Jin Sang Wang, Si Hyun Bae, Seung Kew Yoon
Ji Yeon Baek, Si Hyun Bae, Seung Kew Yoon, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu 137-701, Seoul, Korea
Wonhee Hur, Jin Sang Wang, WHO Collaborating Center for Reference and Research on Viral Hepatitis, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu 137-701, Seoul, Korea
Author contributions: All authors contributed equally to the work.
Supported by the Songeui Foundation of the Catholic University of Korea for Medical Research
Correspondence to: Dr. Si Hyun Bae, Department of Internal Medicine, Kangnam St. Mary’s Hospital, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea. baesh@catholic.ac.kr
Telephone: +82-2-5901425 Fax: +82-2-34814025
Received: September 14, 2006
Revised: October 28, 2006
Accepted: December 28, 2006
Published online: February 28, 2007
Abstract

AIM: To investigate the growth inhibitory mechanism of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7).

METHODS: HepG2 and Huh7 cells were treated with NS-398. Its effects on cell viability, cell proliferation, cell cycles, and gene expression were respectively evaluated by water-soluble tetrazolium salt (WST-1) assay, 4’-6-diamidino-2-phenylindole (DAPI) staining, flow cytometer analysis, and Western blotting, with dimethyl sulfoxide (DMSO) as positive control.

RESULTS: NS-398 showed dose- and time-dependent growth-inhibitory effects on the two cell lines. Proliferating cell nuclear antigen (PCNA) expressions in HepG2 and Huh7 cells, particularly in Huh7 cells were inhibited in a time- and dose-independent manner. NS-398 caused cell cycle arrest in the G1 phase with cell accumulation in the sub-G1 phase in HepG2 and Huh7 cell lines. No evidence of apoptosis was observed in two cell lines.

CONCLUSION: NS-398 reduces cell proliferation by inducing cell cycle arrest in HepG2 and Huh7 cell lines, and COX-2 inhibitors may have potent chemoprevention effects on human hepatocellular carcinoma.

Keywords: Selective cyclooxygenase 2 inhibitor, Cell growth, Cell cycle, Hepatocellular carcinoma cells