蛋白酶体抑制剂MG-132对胃癌细胞株作用的实验研究

目的:探讨蛋白酶体抑制剂MG-132阻断泛素-蛋白酶体通路(ubiquitin-proteasome pathway,UPP)对体外胃癌细胞增殖的抑制作用及其相关机制。方法:将不同浓度的MG-132加入胃癌细胞株SGC-7901中,观察细胞形态变化,并应用MTT法测定细胞抑制效应,流式细胞仪检测细胞凋亡,免疫组化法检测P27kip1的表达。结果:MG-132对胃癌细胞增殖具有显著的抑制作用,瑞氏染色显微镜观察MG-132作用于胃癌细胞后,可见细胞出现细胞质、核仁消失,染色质固缩、边缘化,核膜裂解、染色质分割及大量凋亡小体。5.0μmol/L的MG-132作用24、48h后的凋亡率分别为(16.7±5.1)%和(72.8±16.4)%。免疫组化显示,胃癌细胞在5.0μmol/L的MG-132作用48h后明显表达P27kip-1。结论:MG-132能显著抑制胃癌细胞的增殖,诱导其凋亡。其机制可能为通过上调抑癌蛋白P27kip-1水平而起到抗肿瘤作用。

Effect of Proteasome Inhibitor on Gastric Cancer Cell Line in vitro

Objective To investigate the effect of ubiqutin-proteasome inhibitor MG-132 on human gastric cancer cell line SGC-7901 in vitro and to discuss its mechanism. Methods Gastric cancer cells were cultured with different concentrations of proteasome inhibitor MG-132. The cell growth inhibitory effect was observed by MTT assay. Flow cytometry was used to detect apoptosis and cell cycle change. Expression of P27kip1 was detected by immunocytochemical technique. Results MG-132 possessed an obvious inhibitory effect on gastric cancer cell line in vitro. Typical morphological changes of apoptosis were detected with Wright stain and viewed under microscopy. When treated with 5.0 μmol/L MG-132 for 24 h and 48 h, the rate of cellular apoptosis was（16.7±5.1）% and （72.8±16.4）% respectively. P27kip-1 was highly expressed in the gastric cancer cell line which was treated by 5.0 μmol/L MG-132 for 48 h. Conclusions MG-132 could induce human gastric cancer cell line apoptosis and proliferation inhibition in vitro. The mechanism of its effect might be associated with up-regulated expression of p27kip-1.