维胺酯及其代谢产物的体外活性  

A study of in vitro activities of viaminate and its metabolites

作　　者：傅友军 陶蕾 李玲珺 卜今[4] 马鹏程 

机构地区：[1]南京医科大学第一附属医院 [2]<江苏医药>编辑部,江苏省210029 [3]中国医学科学院皮肤病研究所药物研究室 [4]<南京医科大学学报>编辑部

出　　处：《江苏医药》2014年第21期2528-2531,共4页Jiangsu Medical Journal

摘　　要：目的研究维胺酯及其体内代谢物M1、M2在体外对Hela细胞增殖及维甲酸类受体转录激活的影响。方法采用二甲氧唑黄比色法检测不同浓度的全反式维甲酸(RA)、维胺酯、M1和M2作用96h后对Hela细胞增殖的影响。用脂质体转染法分别将维甲酸受体α(RARα)质粒、RARβ质粒、RARγ质粒、维甲酸X受体α(RXRα)质粒及相应氯霉素乙酰转移酶(CAT)报道质粒共转染到Hela细胞中,分别用1μmol/L的上述4种化合物作用Hela细胞24h后,ELISA法检测各组CAT的表达。结果与对照组相比,100μmol/L的RA、维胺酯和50μmol/L的M1、M2对HeLa细胞的抑制率升高(P<0.05或P<0.01),抗增殖能力大小的顺序为M2>M1>维胺酯>RA。与对照组相比,RA、维胺酯能增加转染RARα、RARβ、RARγ质粒组CAT的表达(P<0.05或P<0.01),而不增加转染RXRα质粒组CAT的表达(P>0.05);M1、M2均不增加转染4种受体质粒组CAT的表达。结论 M1、M2体外抗Hela细胞增殖的能力较维胺酯更强;其机制可能涉及非经典受体途径。Objective To study the effects of viaminate and its two metabolites M1 and M2on the proliferation of Hela cells and transcriptional activation to retinoic acid receptors（RARs）in vitro.Methods The anti-proliferative effects of all-trans-retinoic acid（RA）,viaminate,M1 and M2at different concentrations on Hela cells were measured by XTT assays after incubation for 96 hours.Hela cells were transiently transfected withβRARE-tk-CAT for RARα,βorγplasmid and with TREpal-tk-CAT for RXRαplasmid by liposome-based method.After exposured to the four compounds at a concentration of 1μmol/L for 24 hours,respectively,CAT ELISA was employed to detect the expression of CAT protein.Results Compared with the controls,the inhibition rate to Hela cells was increased with RA and viaminate at 100μmol/L and with M1 and M2at 50μmol/L（P〈0.05 or P〈0.01）.The anti-proliferative activity of the four compounds was in an order of M2 M1viaminate〉RA.Compared with the controls,the expression of CAT protein was increased in Hela cells transfected with RARα,βorγplasmid followed by RA and viaminate treatment（P〈0.05 or P〈0.01）,but not transfected with RXRαplasmid followed by RA and viaminate treatment and the four above receptor plasmids followed by M1 and M2treatment（P〉0.05）.Conclusion The antiproliferative activity of M1 and M2to Hela cells in vitro is stronger than that of viaminate.The machenism for this may be involved in a RARs-independent pathway.

关 键 词：维胺酯 维甲酸类受体 

分 类 号：R962[医药卫生—药理学]