蛋白酶体抑制剂单用或联合顺铂对人胃癌细胞的抑制效应  

Inhibitory Effect of Proteasome Inhibitor Alone or in Combination with Cisplatin on Human Gastric Cancer Cells

作　　者：李真真[1] 靖大道[2] 丁红华[1] 

机构地区：[1]上海交通大学附属第一人民医院肿瘤科,200080 [2]上海交通大学附属第一人民医院消化科,200080

出　　处：《胃肠病学》2008年第12期733-736,共4页Chinese Journal of Gastroenterology

摘　　要：背景:蛋白酶体抑制剂通过阻断泛素-蛋白酶体通路中的蛋白降解,致使错误折叠蛋白或受破坏蛋白堆积,启动热休克反应并进一步导致细胞死亡,对多种恶性肿瘤细胞具有抑制作用。目的:探讨蛋白酶体抑制剂Z-Leu-Leu-Phe-CHO(ZLLFC)单用或联合顺铂对人胃癌细胞株SGC-7901体外增殖和凋亡的影响及其对肿瘤多药耐药相关切除修复交叉互补基因1(ERCC1)mRNA表达的影响。方法:将ZLLFC和顺铂单独或联合作用于SGC-7901细胞,以甲基噻唑基四唑(MTT)法检测细胞存活率,透射电子显微镜观察凋亡细胞形态,流式细胞仪检测细胞凋亡率,逆转录聚合酶链反应(RT-PCR)检测ERCC1mRNA表达。结果:ZLLFC或顺铂单独作用后,SGC-7901细胞存活率较对照组显著降低(P<0.01),呈现轻度凋亡形态;ZLLFC联合顺铂组细胞存活率较单用顺铂组显著降低(P<0.01),细胞凋亡率显著升高(P<0.01),呈现明显凋亡形态。联合组ERCC1mRNA表达显著低于单用顺铂组(P<0.01)。结论:蛋白酶体抑制剂ZLLFC能轻度抑制人胃癌细胞株SGC-7901生长,诱导细胞凋亡,与顺铂联用具有协同抑制效应。ZLLFC可能通过下调ERCC1转录水平逆转顺铂耐药,从而增强顺铂的抗肿瘤作用。Background： Proteasome inhibitors block the degradation of protein in ubiquitin-proteasome pathway, causing the accumulation of misfolding and damaged proteins and initiating the heat shock response, thereby leading to ceils death. Growth of various malignant tumor ceils could be inhibited by proteasome inhibitors. Aims： To investigate the effect of proteasome inhibitor Z-Leu-Leu-Phe-CHO （ZLLFC） alone or in combination with cisplatin on the proliferation and apoptosis of human gastric cancer cell line SGC-7901 in vitro and the mRNA expression of multidrug resistance-related excision repair cross-complement group 1 （ERCC1） gene. Methods： SGC-7901 cells were treated with ZLLFC, cisplatin alone or in combination. Methyl thiazolyl tetrazolium （MTT） assay was used to assess the survival rate of SGC-7901 cells. The morphology of apoptotic cells was observed under transmission electron microscope, and the apoptosis rate was assessed by flow cytometry. Expression of ERCC1 mRNA was determined by reverse transcriptase polymerase chain reaction （RT-PCR）. Results： ZLLFC or cisplatin alone could inhibit the proliferation of SGC-7901 cells, the survival rate was significantly lower than that of controls （P〈0.01）, and mild apoptotic features were observed under electron microscope. Combined use of ZLLFC and cisplatin significantly decreased further the survival rate of SGC-7901 cells and increased the apoptosis rate （P〈0.01）, the cells presented typical apoptotic morphology. Expression of ERCC1 mRNA in combined group was significantly lower than that of cisplatin alone group （P〈0.01）. Conclusions： Proteasome inhibitor ZLLFC can modestly inhibit the growth of human gastric cancer cell line SGC-7901 and induce cell apoptosis. A synergistic effect is achieved when ZLLFC is combined with cisplatin. ZLLFC might reverse the cisplatin resistance by down-regulating ERCC1 transcription, thereby enhances the anti-tumor effect of cisplatin.

关 键 词：蛋白酶体抑制剂 顺铂 胃肿瘤 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]