文献类型：期刊文献

中文题名：维生素C衍生物对癌细胞浸润转移能力的抑制作用机理研究

英文题名：STUDY ON THE MECHANISM OF INHIBITION OF TUMOR CELL MOTILITY BY ASCORBIC ACID DERIVATIVES

作者：刘建文[1];魏东芝[1];杜长斌[1];三羽信比古[2]

机构：[1]华东理工大学生物反应器国家重点实验室生物化学研究所,上海200237;[2]广岛县立大学生物资源学部细胞生物学研究室

年份：2002

卷号：35

期号：2

起止页码：82

中文期刊名：实验生物学报

外文期刊名：Acta Biologiae Experimentalis Sinica

收录：MEDLINE(收录号：15344324);;北大核心:【北大核心2000】；CSCD:【CSCD2011_2012】；PubMed;

基金：上海市重点学科资助项目

语种：中文

中文关键词：维生素C衍生物;癌细胞浸润转移能力;抑制作用;机理

外文关键词：Ascorbic acid. Invasion. Metastasis. Reactive oxygen species

摘要：前期研究表明Asc2P6P1m能够有效地抑制癌细胞的浸润转移。本文试图以Asc2P6P1m对人成纤维瘤细胞浸润转移作用探讨维生素C衍生物对癌细胞转移能力抑制的机理。对HT-1080细胞分别以50—300μmol/LAsc2P6P1m处理1h,随着Asc2P6P1m浓度的增大,细胞移动的数目明显减少,Asc2P6P1m对HT-1080细胞移动的抑制作用呈现出量效关系。Asc2P6P1m对ROS的清除作用,通过自旋捕集剂DMPO以电子自旋共振方法进行研究。HT-1080细胞经Asc2P6P1m处理后,细胞内的自由基水平与对照组相比有显著的降低。用F-actin的分子探针NBD研究表明,随处理时间延长,细胞内荧光强度与对照组相比显著降低。Western blots研究表明,细胞核内的RhoA蛋白量随Asc2P6P1m处理时间延长而逐渐增加。研究提示,Asc2P6P1m对癌细胞浸润转移能力的抑制作用是与抑制癌细胞内的ROS、提高细胞核内RhoA水平、降低细胞质内F-actin相关。
Our previous study shows that tumor invasion is inhibited by 2-O-phosphorylated ascorbate-6-O-palmitylester (Asc2P6Plm). In the present study, the mechanism underlying the inhibitory effect of Asc2P6Plm on invasion of human fibrosarcoma cells HT-1080 was attempted to be analysed. Migratory ability of the tumor cells was shown to be inhibited in a dose-dependent manner by treatment with Asc2P6Plm at 50 -300 μmol/L for 1 hr. Hydroxyl radicals in homogenates of Asc2P6Plm-treated HT-1080 cells were markedly diminished relative to those of non-treated cells as evaluated by electron spin resonance method using the spin-trapping agent DMPO. F-actin was localized in the vicinity of the cell membrane abundantly in nontreated cells, but was diminished in a time-dependent manner in Asc2P6Plm-treated cells as shown with the F-actin-di-rected agent NBD-phallacidin. The cell adhesion-controlling molecule RhoA increased time-dependently in the cell nucleus of Asc2P6Plm-treated cells as shown by Western blots. Thus the inhibition of tumor invasion by Asc2P6Plm was shown to be attributed to decreases in both the cell migratory ability and the F-actin localization near the cell membrane, which may result from an increase in RhoA in the cell nucleus and reduction of in-tracellular ROS that is achieved by enrichment of intracellular Asc derived from Asc2P6Plm.