戊地昔布诱导人食管癌Eca109细胞凋亡的机制研究  

Induction and mechanism of valdecoxib on the apoptosis of human esophageal cancer cells

作　　者：张玉军[1] 刘淑霞[1] 齐凤英[1] 左连富[2] 郭建文[2] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017 [2]河北省肿瘤研究所流式细胞室,河北石家庄050011

出　　处：《中国药理学通报》2006年第5期629-633,共5页Chinese Pharmacological Bulletin

基　　金：河北省自然科学基金资助项目(No301354)

摘　　要：目的探讨特异选择性环氧化酶-2（COX-2）抑制剂戊地昔布诱导人食管癌Eca109细胞凋亡及其作用机制。方法流式细胞术检测细胞凋亡和细胞周期分布；电子显微镜进一步检测细胞凋亡；采用乳酸脱氢酶（LDH）试剂盒测定Eca109细胞的LDH含量；流式细胞术检测p-p38MAPK及凋亡基因Fas和FasL蛋白的表达。结果戊地昔布（25—400μmol·L^-1）可诱导人食管癌Eca109细胞发生凋亡，凋亡率由（2．95±0．83）％增力口到（48．46±0．73）％；50—400μmol·L^-1时增殖指数和S期的细胞比例则明显降低，G0／G1期的细胞比例增加；同时，流式细胞术显示，25μmol·L^-1戊地昔布即可上调人食管癌Eca109细胞p-p38MAPK蛋白的表达，并随剂量的增加而增强；50—400μmol·L^-1的戊地昔布可上调Eca109细胞Fas及FasL的表达。结论戊地昔布可诱导人Eca109细胞凋亡，其诱导凋亡的机制可能部分是通过激活p-p38MAPK／Fas、FasL途径实现的。Aim To investigate the effect and mechanism of valdecoxib on the apoptosis of human esophageal cancer ceils. Methods Flow cytometry was used to observe the effect of valdecoxib on apoptosis and the cell cycle distribution of Eca109 ceils. Transmission electron microscope was further used to detect the cell apoptosis. The content of LDH was examined using LDH kit. The expressions of p-p38MAPK, Fas and FasL protein were detected using flow cytometry. Resuits Valdecoxib of 25 -400 μmol · L^-1 significantly induced the apoptosis of Eca109 cell line , and the rate of apoptosis was increased from （2.95 ± 0. 83 ） % to （48.46 ±0. 73）%, 50-400μmol · L^-1 valdecoxib also decreased the proliferation index and the proportion of cells in the S phase, increased the proportion of ceils in the G0/G1 phase, but had no effect on the proportion of cells in the G2/M phase. Compared with those in Ecal09 cells cultured in the medium with solvent, the expression of p-p38MAPK ,Fas and FasL was higher in the Eca109 cells exposed to valdecoxib in a dose-dependent manner in 72 h. Conclusion Valdecoxib can induce apoptosis of Eca109 cell line partly by up-regulating the expression of p-p38MAPK/Fas/ FasL.

关 键 词：戊地昔布 人食管癌Eca109细胞 凋亡 P-P38MAPK FAS FASL 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R73-351[医药卫生—基础医学]