文献类型：期刊文献

中文题名：新型靶向组蛋白去乙酰化酶抑制剂的抗肿瘤作用及其机制

英文题名：Antitumor effects and molecular mechanisms of novel selective HDAC inhibitors in human cervix carcinoma HeLa cells

作者：金惠[1,2];刘力锋[2];邓卫平[2];刘建文[2]

机构：[1]同济大学生命科学与技术学院,上海200092;[2]华东理工大学生物反应器国家重点实验室&药学院,上海200237

年份：2013

卷号：44

期号：4

起止页码：352

中文期刊名：中国药科大学学报

外文期刊名：Journal of China Pharmaceutical University

收录：CSTPCD;;Scopus;北大核心:【北大核心2011】；CSCD:【CSCD2013_2014】；

基金：中国博士后基金资助项目(No.2013M531221);上海市科学技术委员会基础研究重点项目资助(No.09JC1404500)~~

语种：中文

中文关键词：组蛋白去乙酰化酶抑制剂;HDAC-1;咔啉骨架;乙酰化组蛋白H3;p21cip;WAF;抗肿瘤

外文关键词：histone deacetylase inhibitor; HDAC-1; carboline structure; acetylated-H3; p21cip/WAF; antitumor

摘要：探讨3种新型靶向组蛋白去乙酰化酶(HDAC)抑制剂D16,D22,D29的抗肿瘤活性作用及其抑制人宫颈癌细胞增殖的机制。MTT法检测D16,D22,D29对MCF-7、HCT-116、A549、HeLa以及K562的增殖抑制作用;测定D16,D22,D29对HDAC及其HDAC-1的酶活抑制作用;流式细胞术观察D16,D22,D29对HeLa细胞周期及凋亡诱导作用;Western blot测定D16,D22,D29对HeLa细胞中乙酰化组蛋白H3(Ac-H3),p21cip/WAF的蛋白表达影响。结果显示,D16,D22,D29明显抑制多种肿瘤细胞株的增殖,有效抑制HDAC及其HDAC-1的活性,其效果优于阳性对照药Vorinostat(SAHA),并诱导HeLa细胞产生G1期细胞周期阻滞及凋亡,Ac-H3及p21cip/WAF的蛋白水平明显上升。D16,D22,D29具有一定的抗肿瘤活性,其机制与诱导细胞周期阻滞和凋亡产生,促进p21cip/WAF的蛋白表达有关。
Examine the antitumor activity of three new histone deacetylase（HDAC） and HDAC-1 inhibitors with the carboline structure named D16,D22,D29 and explore the molecular mechanisms underlying.The anti-proliferative effects were detected by MTT assays in MCF-7,HCT-116,A549,HeLa and K562.The inhibition in HDAC and HDAC-1 were detected by using fluorescent substrate.The effects on the cell cycle arrest and apoptosis induction were examined by flow cytometry.The protein expressions of acetylated-H3 and p21cip/WAF were detected by Western blotting.D16,D22,and D29 inhibited the proliferation of multiple carcinoma cells at much lower concentrations than SAHA dose-dependently.D16,D22,D29 effectively inhibited the activity of HDAC and HDAC-1;D16,D22 and D29 induced G1 phase cell cycle arrest and apoptosis while the protein expression of acetylation of histone H3 and p21cip/WAF were significantly up-regulated.D16,D22 and D29 were potent antitumor agents with their cycle arrest and apoptosis mechanisms.The molecualar mechanisms were associated with the promotion of acetylated-H3 and p21cip/WAF.