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

Selective COX-2 inhibitor, NS-398, suppresses cellular proliferation in human hepatocellular carcinoma cell lines via cell cycle arrest
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DOI:
10.3748/wjg.v13.i8.1175
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发表时间:
2007-02-28
影响因子:
4.3
通讯作者:
Ybon, Seung Kew
Ybon, Seung Kew
中科院分区:
医学2区
文献类型:
--
作者:
Baek, Ji Yeon;Hur, Wonhee;Ybon, Seung Kew

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目的:目的:探讨选择性环氧化酶2(考克斯-2)抑制剂NS-398对肝癌细胞株HepG 2和Huh 7生长的抑制机制。以二甲基亚砜(DMSO)为阳性对照,采用四唑盐(WST-1)法、DAPI染色法、流式细胞仪和Western blotting法分别观察NS-398对细胞活力、细胞增殖、细胞周期和基因表达的影响。HepG 2和Huh 7细胞增殖细胞核抗原(PCNA)表达均受到抑制,尤以Huh 7细胞为甚,且呈时间和剂量依赖性。NS-398在HepG 2和Huh 7细胞系中引起G1期细胞周期停滞,并在亚G1期细胞积聚。结论:NS-398通过诱导HepG 2和Huh 7细胞周期阻滞抑制细胞增殖,提示考克斯-2抑制剂可能对人肝癌具有化学预防作用。(C)2007年,WJG出版社。All rights reserved.
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 close- 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. (C) 2007 The WJG Press. All rights reserved.