选择性环氧合酶-2抑制剂NS-398对人肝癌细胞株HepG2增殖和凋亡的影响

目的探讨选择性环氧合酶-2抑制剂NS-398对人肝癌HepG2细胞株的生长抑制、诱导凋亡及其对bcl-2表达的影响。方法采用MTT法检测细胞增殖，流式细胞术检测细胞周期、凋亡及凋亡相关蛋白bcl-2的表达。结果NS-398抑制HepG2的增殖活性，经20、40、80和160μmol／L的NS-398处理细胞48h后，其抑制率分别为6．72％、16．21％、20．86％和25．34％，呈剂量依赖效应关系；细胞经160bLmol／L的NS-398处理24h、48h和72h后，G。／G1期细胞由76．07±0．75％分别减少至62．27±0．74％、59．17±1．47％和53．03±1．60％（P〈0．05），S期细胞由11．40±0．79％分别增加至13．23±0．81％、16．20±1．95％和16．60±1．25％（P〈0．05），G2／M期细胞无明显变化；凋亡细胞增多，凋亡率分别为8．47％、16．3％和23．9％；细胞经160μmol／L的NS-398处理48h后bcl-2蛋白与对照组比，表达下调（P〈0．01）。结论NS-398对人肝癌细胞株HepG2有抑制增殖、诱导凋亡作用，细胞凋亡的机制可能与细胞凋亡相关基因bcl-2表达下调有关。

Effect of NS -398 on the proliferation and apoptosis of HepG2 cell line

Objective To investigate the effects of NS-398,an cyclooxygenase-2 selective inhibitor,on the proliferation and apoptosis of HepG2 cells. Methods The proliferation of cells was detected by MTT assay. The cell cycle and apoptosis associated with bcl-2 were detected by flow cytometry. Results NS-398 inhibited the proliferation of human HepG2 cells at a dose-dependent manner. When interfered with NS-398 at a dose of 20,40,80 and 160μmol/L for 48h, the inhibiting rates were 6.72% ,16.21% ,20.86% and 25.34% ,respectively; and when interfered with 160μmol/L NS-398 for 24h,48h and 72h,the cells of G0/G1 from 76.07± 0.75% reduced to 62.27±0. 74%,59.17± 1.47% and 53.03± 1. 600/60 ,respectively（P 〈0.05） ; the cells of S stage from 11.40±0. 790/60 increased to 13.23±0.81% ,16.20±1. 950/60 and 16.60±1.25 %,respectively（P〈0.05）. The cell of G2/M stage was not markedly changed; The apoptotic cells increased with the apoptosis rates of 8.47 0/60,16.3 0/60 and 23.9 0/60, respectively. The expression of bcl-2 decreased obviously as compared with control group（P〈0. 01）. Conclusion NS-398 can inhibit the proliferation and induce apoptosis of HepG2,which might be related to the down regulated expression of bcl-2.