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Antimetastatic effect of prodigiosin through inhibition of tumor invasion  ( SCI-EXPANDED收录)  

文献类型:期刊文献

英文题名:Antimetastatic effect of prodigiosin through inhibition of tumor invasion

作者:Zhang, J; Shen, YL; Liu, JW; Wei, DZ

机构:[1]E China Univ Sci & Technol, Dept Mol & Cellular Pharmacol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份:2005

卷号:69

期号:3

起止页码:407

外文期刊名:BIOCHEMICAL PHARMACOLOGY

收录:;WOS:【SCI-EXPANDED(收录号:WOS:000226699800005)】;

语种:英文

外文关键词:prodigiosin; metastasis; invasion; MMPs; RhoA

摘要:Prodigiosin, a bacterial metabolite, was reported to have immunosuppressive and anticancer activities. In this study, we investigated novel functions of prodigiosin about anti-metastasis and anti-invasion. Prodigiosin dose-dependently inhibited 95-D cells' migration and invasion according to wound healing assay and the Transwell assay. The inhibitive effect could reach about 50% when cells were treated with 5 muM prodigiosin for 12 h. In animal experiment, intraperitoneal administration of 5 mg kg(-1) prodigiosin decreased the number of metastatic nodules by 53% and elevated the survival rate of mice about one-fold comparing with control group. Results of cell aggregation and adhesion assay showed that prodigiosin could promote cell aggregation and simultaneously inhibit cell from adhering to extracellular matrix (ECM). In addition, prodigiosin suppressed RhoA gene expression, hence, decreased protein level of RhoA in 95-D cells, according to RT-PCR assay and Western blot assay. Gel zymogram assay revealed that prodigiosin could suppress the activity of matrix metalloproteinase-2 (MMP-2). These results demonstrate that prodigiosin effectively inhibit tumor metastasis in vitro and in vivo. The action mechanisms of prodigiosin are associated with the promotion of cell aggregation and the inhibition of various steps in cell invasive process, which include the inhibition of cell adhesion and mobility in a RhoA-dependent way and the suppression of MMP-2 ability. (C) 2004 Published by Elsevier Inc.

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