標題: | The molecular mechanism of actinomycin D in preventing neointimal formation in rat carotid arteries after balloon injury |
作者: | Wu, CH Pan, JS Chang, WC Hung, JS Mao, SJT 生物科技學系 Department of Biological Science and Technology |
關鍵字: | actinomycin D;neointimal formation;proliferation;restenosis |
公開日期: | 1-五月-2005 |
摘要: | The pathological mechanism of restenosis is primarily attributed to excessive proliferation of vascular smooth muscle cells (SMC). Actinomycin D has been regarded as a potential candidate to prevent balloon injury-induced neointimal formation. To explore its molecular mechanism in regulating cell proliferation, we first showed that actinomycin D markedly reduced the SMC proliferation via the inhibition of BrdU incorporation at 80 nM. This was further supported by the G1-phase arrest using a flowcytometric analysis. Actinomycin D was extremely potent with an inhibitory concentration IC50 at 0.4 nM, whereas the lethal dose LD50 was at 260 mu M. In an in vivo study, the pluronic gel containing 80 nM and 80 lMactinomycin D was applied topically to surround the rat carotid adventitia; the thickness of neointima was substantially reduced (45 and 55%, respectively). The protein expression levels of proliferating cell nuclear antigen ( PCNA), focal adhesion kinase (FAK), and Raf were all suppressed by actinomycin D. Extracellular signal-regulated kinases (Erk) involved in cell-cycle arrest were found to increase by actinomycin D. These observations provide a detailed mechanism of actinomycin D in preventing cell proliferation thus as a potential intervention for restenosis. |
URI: | http://dx.doi.org/10.1007/s11373-005-6900-5 http://hdl.handle.net/11536/13776 |
ISSN: | 1021-7770 |
DOI: | 10.1007/s11373-005-6900-5 |
期刊: | JOURNAL OF BIOMEDICAL SCIENCE |
Volume: | 12 |
Issue: | 3 |
起始頁: | 503 |
結束頁: | 512 |
顯示於類別: | 期刊論文 |