NS-398 诱导肝癌细胞凋亡的实验研究

目的: 研究选择性环氧化酶-2(COX-2) 抑制剂NS-398 对人肝癌细胞HepG₂ 凋亡的影响, 及其相关蛋白Bcl-2 在细胞凋亡中的作用。方法: 通过体外细胞培养, 应用荧光显微镜、透射电镜、流式细胞仪观察NS-398 对HepG₂ 的凋亡诱导作用, 应用免疫细胞化学法观察Bcl-2 在人肝癌细胞HepG₂ 凋亡中的表达。结果: NS-398 处理HepG₂ 细胞后, 电镜下可见到细胞核固缩、染色质凝集成新月型紧靠核膜周边,核碎裂、染色质片断化等典型的细胞凋亡形态变化。荧光显微镜及流式细胞检测则未见凋亡征象。免疫细胞化学分析显示, NS-398 处理后的HepG₂ 细胞,其Bcl-2 表达较对照组明显下降。结论: COX-2 选择性抑制剂NS-398 对人肝癌HepG₂ 细胞有显著的凋亡诱导作用;抗凋亡基因Bcl-2 在NS-398 诱导的HepG₂ 细胞凋亡中有重要的调控作用。

Experimental study on apoptosis of HepG2 cell induced by NS-398

AIM: To study the effects of selective COX-2 inhibitor NS-398 on apoptosis of HepG₂ cell line and to evaluate the modulation activity of Bcl-2 on the procession of HepG₂ cell apoptosis.METHODS: HepG₂ cells were cultured in RPMI1640 media and treated by NS-398 for 24, 48 and 72 hours.The apoptosis of HepG₂ cells was observed by fluorescent microscopy, transmission electronmicroscopy and flow cytometric analysis.The expression of Bcl-2 in HepG₂ cells during the apoptosis was measured by immunocellularchemical staining.RESULTS: NS-398 obviously induced some morphologic features of HepG₂ cell apoptosis such as cellular nucleus shrinking, nucleus fragments, luniform chromatin agglutinating and chromatin fragmentation.Compared with the control group, the NS-398 group significantly decreased the expression of Bcl-2.CONCLUSION: COX-2 selective inhibitor NS-398 can significantly induce the apoptosis of hepG₂ cells, and Bcl-2 may play an important role in modulating apoptosis induced by NS-398.