JNK抑制剂对D-氨基葡萄糖衍生物诱导人食管癌Eca-109细胞周期阻滞和凋亡的影响  

Effect of JNK inhibitor on apoptosis and cell cycle arrest of human esophageal cancer cell line Eca-109 induced by the derivative of D-amine-glucose

作　　者：强占荣[1] 吴静[2,1] 杨国栋[1] 李娟[1] 周永宁[1] 王爱勤[3] 薛群基[3] 

机构地区：[1]兰州大学第一医院消化科,甘肃兰州730000 [2]北京世纪坛医院北京大学第九临床医学院消化科,北京100038 [3]中国科学院兰州化学物理研究所,甘肃兰州730000

出　　处：《基础医学与临床》2009年第3期259-263,共5页Basic and Clinical Medicine

基　　金：中国科学院西部之光项目(NOCX805)

摘　　要：目的观察特异性C-JUN氨基末端激酶(JNK)抑制剂SP600125对D-氨基葡萄糖衍生物2-(3-羧基-1-丙酰氨基)-2-脱氧-D-葡萄糖(COPADG)诱导的Eca-109细胞凋亡和细胞周期阻滞的影响,并探讨COPADG诱导Eca-109细胞凋亡的潜在分子机制。方法体外培养Eca-109细胞,以COPADG及SP600125与细胞作用;Western blot法检测P-JNK蛋白表达,MTT法检测细胞增殖,流式细胞术检测细胞周期。结果COPADG显著增加Eca-109细胞P-JNK蛋白的表达和细胞凋亡率,且诱导Eca-109细胞发生G0/G1期细胞阻滞,SP600125明显减少Eca-109细胞凋亡,并使G0/G1期细胞阻滞向G2/M期细胞阻滞发展。结论COPADG可能通过激活JNK信号通路诱导Eca-109细胞凋亡。Objective To explore the effect of SP600125, a specific C-JUN NH2 terminal protein kinase （JNK） inhibitor, on apoptosis and cell-cycle arrest of the human esophageal cancer cell line Eca-109 induced by 2-（3- carboxy-1-oxopropyl） amino-2-deoxy-D-Glucose （COPADG）and potential molecular mechanism in COPADG-induced cell apoptosis was discussed. Methods Eca-109 cells were cultured and then pre-incubated with SP600125 for 30 min prior to exposure to COPADG of different concentrations and for different times. Changes of expression of P-JNK protein were examined by Western blot;Cell growth Apoptosis and cell-cycle arrest were analyzed by flow inhibitory rate was detected by MTT colorimetric assay; cytometry. Results COPADG significantly inhibited proliferation of Eca-109 cells and induced them into apoptosis and cell-cycle arrest in G0/G1 phase. Western blot showed that the protein expression of P-JNK was increased in a dose-dependent manner in Eca-109 cells after stimulation by COPADG. SP600125 remarkablely inhibited the protein expression of P-JNK as well as the apoptosis rate and cell growth inhibitory rate in Eca-109 cells induced by COPADG as compared with those treated with only COPADG, meanwhile, cell-cycle arrest in G0/G1 phase progressed to cell-cycle arrest in G2/M phase. Conclusion JNK sig- naling pathway may play an important role in apoptosis of Eca-109 induced by the COPADG.

关 键 词：2-(3-羧基-1-丙酰氨基)-2-脱氧-D-葡萄糖 食管癌 凋亡 C-JUN氨基末端激酶 细胞周期阻滞 

分 类 号：R735.1[医药卫生—肿瘤]