4-氨基-2-三氟甲基苯基维甲酸酯对肝癌细胞株HepG2增殖凋亡分化的影响  

Effect of a synthetic retinoid on proliferation and apoptosis of HepG2 and the mechanisms for apoptosis

作　　者：张海涛[1] 何苇[1] 桂淑玉[2] 陈飞虎[3] 李庆[1] 江志奎[1] 左莉[1] 周青[1] 汪渊[1] 

机构地区：[1]安徽医科大学分子生物学实验室和生物化学与分子生物学教研室,省部共建教育部和安徽省重要遗传病基因资源利用重点实验室,合肥230032 [2]安徽医科大学第一附属医院呼吸内科,合肥230022 [3]安徽医科大学药学院,合肥230032

出　　处：《安徽医科大学学报》2010年第2期204-208,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:090413116)

摘　　要：目的研究新合成的全反式维甲酸(ATRA)衍生物(4-氨基-2-三氟甲基苯基维甲酸酯)对人肝癌细胞株HepG2体外增殖、凋亡及分化情况的影响。方法3种浓度(1、5、10μmol/L)的ATRA衍生物分别处理HepG2细胞,1、2、3、7d后用MTT法检测4-氨基-2-三氟甲基苯基维甲酸酯对HepG2细胞增殖的影响;酶动力学法检测γ-谷氨酰转肽酶(γ-GT)比活性和甲胎蛋白(AFP)分泌量变化;流式细胞术分析细胞周期及凋亡情况;Western blot检测HepG2细胞中凋亡相关蛋白的表达量。结果10μmol/L的4-氨基-2-三氟甲基苯基维甲酸酯可明显诱导HepG2细胞凋亡,凋亡率达到49%,并且使代表肝细胞恶变的γ-GT比活性、AFP分泌量明显下降,Western blot显示4-氨基-2-三氟甲基苯基维甲酸酯显著抑制Bcl-2、Bcl-xS/L和p-Erk表达。结论4-氨基-2-三氟甲基苯基维甲酸酯是肝癌细胞HepG2有效的分化诱导剂,并明显促进肝癌细胞凋亡。Objective To investigate the effect of a synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester on proliferation and apoptosis of HepG2 and the mechanisms of apoptosis.Methods The cell proliferation of HepG2 was analyzed by MTT assay.Light microscope was used to observe morphologic changes,and the diversity of γ-glutamyl transpeptidase （γ-GT） and alpha-fetoprotein（AFP） were detected by kinetics analysis.Flow cytometry was uesd to study the effects on cell cycle and apoptosis.The expression of apoptosis-related protein were studied by Western blot.Results 4-amino-2-tri-fluoromethyl-phenyl ester could inhibite growth of HepG2 cells after a short time treated with a concentration-dependent manner.Moreover,the specific activities of γ-GT and the secretary amount of AFP significantly decreased.It induced apoptosis with the decreased expression of Bcl-2,Bcl-xS/L.Conclusion 4-amino-2-tri-fluoromethyl-phenyl ester works rapidly,and is superior to ATRA in the same concentration at the same action time.

关 键 词：肝肿瘤 细胞凋亡 细胞分化 

分 类 号：R735.7[医药卫生—肿瘤] R986[医药卫生—临床医学]