新型全反式维甲酸衍生物4-氨基-2-三氟甲基苯基维甲酸酯对肝癌细胞株HepG2增殖的影响  

Effects of a novel all-trans retinoid acid derivative 4-amino-2-trifluoromethyl-phenyl retinate on the proliferation of HepG2 cells

作　　者：刘慧[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、生物化学与分子生物学教研室、安徽省/省部共建教育部重要遗传病基因资源利用重点实验室,合肥230032

出　　处：《安徽医科大学学报》2016年第2期156-160,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81272399);安徽省自然科学基金(编号:090413116)

摘　　要：目的研究4-氨基-2-三氟甲基苯基维甲酸酯(ATPR)对人肝癌细胞株Hep G2增殖的影响,并初步探讨其可能的作用机制。方法选取Hep G2细胞为研究对象,全反式维甲酸(ATRA)和ATPR分别作用细胞,应用MTT比色法测定细胞增殖,流式细胞术检测细胞周期分布情况,Western blot法检测Hep G2细胞内周期蛋白D(cyclin D)及细胞周期蛋白依赖性激酶4(CDK4)和CDK6蛋白表达量。结果ATPR能够显著抑制Hep G2细胞的增殖,将细胞阻滞在G0/G1期,呈浓度与时间依赖性(P<0.05),并且同浓度、同一处理时间下,ATPR的抑制率更高(P<0.05);此外,Western blot结果显示,ATPR较ATRA更能显著下调Hep G2细胞中cyclin D和CDK6蛋白表达水平(P<0.05),而CDK4蛋白水平在各组变化均不明显。结论同等浓度下,ATPR抑制Hep G2细胞增殖的效果明显强于ATRA,其机制可能是ATPR通过下调cyclin D和CDK6蛋白的表达水平,造成G0/G1期阻滞,最终导致肝癌细胞株Hep G2的增殖抑制。Objective To explore the effects of 4-amino-2-trifluoromethyl-phenyl retinate （ATPR） on the proliferation of human hepatocellular carcinoma （HCC） HepG2 cells and preliminarily clarify the probable mechanisms. Methods HepG2 cells were used as the research model and treated with all-trans retinoic acid （ATRA） and ATPR respectively. The viability of HepG2 cells was investigated by MTF assay. Flow eytometry was used to detect cell cycle distribution. The expression of cyelinD, eyelin-dependent kinase 4 （CDK4） and CDK6 proteins in HepG2 cells were detected by Western blot. Results ATPR significantly inhibited the proliferation of HepG2 cells in a dose- and time-dependent manner compared with cell group and arrested cells on G0/G1 phase （ P 〈 0. 05 ）. The inhibition rate of ATPR was much higher than that of ATRA at the same dose for the indicated time （P 〈 0. 05 ）. In addition, Western blot results showed that ATPR down regulated the expression of cyelinD and CDK6 more dramatically than ATRA （P 〈 0. 05 ） , while CDK4 expression was constant in all groups. Conclusion ATPR exhibits a better inhibitory effect on HepG2 cells proliferation than ATRA. The mechanism may be partly through down regulating the expression of eyelinD and CDK6 to cause G0/G1 arrest, which finally leads to growth inhibition.

关 键 词：肝癌 HEPG2细胞 全反式维甲酸 4-氨基-2-三氟甲 基苯基维甲酸酯 细胞周期 细胞增殖 

分 类 号：R735.7[医药卫生—肿瘤] R966[医药卫生—临床医学]