文献类型：期刊文章

作　　者：张国州[1] 熊堃[1] 马薇薇[1] 徐伟[1] 曾慧慧[1]

机构地区：[1]北京大学医学部药学院化学生物学系,天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》

基　　金：National Natural Science Foundation(Grant No.81372266);National Science and Technology Major Project,People’s Republic of China(Grant No.2011zx09101-001-03)

年　　份：2016

卷　　号：25

期　　号：4

起止页码：302-309

语　　种：中文

收录情况：CAB、CAS、CSCD、CSCD2015_2016、DOAJ、EMBASE、IC、JST、SCOPUS、ZGKJHX、普通刊

摘　　要：As a synthesized antineoplastic organoselenium compound, ethaselen is known to induce apoptosis in tumor cells via dose-dependent thioredoxin reductase （TrxR） inhibition. Thioredoxin, the multifunctional biological substrate of TrxR, is then left in the oxidized state, which subsequently leads to intracellular accumulation of reactive oxygen species （ROS）, cell cycle arrest and/or apoptosis. However, the low dose effect of ethaselen remains largely unknown. Several subclones have been derived from HepG2 cells by using single cell or colony isolation. The low dose of ethaselen was defined as the drug concentration of retaining 〉90% HepG2 cells alive. The HepG2 cells were used as reference of its subclones （SM01, SM02 and SM03）, and the cell cycle transition, intracellular proteins change, colony formation and sphere growth were assayed in treatment of low dose ethaselen. HepG2 and its subclones differently responded to lethal dose of cisplatin or 5-fluorouracil. Low dose of ethaselen （1 μm） modulated the cell cycle transition at 12 h of treatment, but ceils were partially recovered at 24 h of treatment though some proteins were still affected. Low dose of ethaselen did not inhibit the small colony （diameter 〉 100 μm） formation and sphere growth of HepG2 and SM01. However, low dose of ethaselen could specifically inhibit the survival, large colony （diameter 〉500 μm） formation and sphere growth of SM03, although SM03 could be rapidly recovered from ethaselen-induced cell cycle check. HepG2 and its subclone cells could survive but respond differently to treatment of low dose ethaselen （1 μM）. Low dose of ethaselen could significantly inhibit a HepG2 subclone （SM03） in cell survival and colony growth.

关 键 词：Low dose  ORGANOSELENIUM Ceil subcloning  HETEROGENEITY Tumor cell  

分 类 号：R96]