Selective COX-2 inhibitor, NS-398, suppresses cellular proliferation in human hepatocellular carcinoma cell lines via cell cycle arrest

• Published in: World journal of gastroenterology : WJG 2007-02, Vol.13 (8), p.1175-1181
• Main Authors: Baek, Ji Yeon, Hur, Wonhee, Wang, Jin Sang, Bae, Si Hyun, Yoon, Seung Kew
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Humans; Liver Cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Nitrobenzenes - pharmacology; Nitrobenzenes - therapeutic use; NS-398; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; 细胞周期阻滞; 细胞增殖; 肝细胞癌细胞系; 选择性COX-2抑制剂
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v13.i8.1175

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.