標題: Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation
作者: Kuo, Wei-Wen
Weng, Jing-Ru
Huang, Chih-Yang
Tsai, Chang-Hai
Liu, Wei-Hung
Wen, Cheng-Hao
Tsai, Shih-Chang
Wu, Chieh-Hsi
生物科技學系
Department of Biological Science and Technology
關鍵字: Restenosis;OSU-03012;Percutaneous transluminal coronary angioplasty (PTCA);Migration;Vascular smooth muscle cell (VSMC) proliferation
公開日期: 1-Nov-2010
摘要: Restenosis is resulted from the proliferation and migration of vascular smooth muscle cells (VSMCs) from the arterial media into the intima within the vessel lumen following percutaneous transluminal coronary angioplasty (PTCA). OSU-03012, a synthetic compound (2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide) acting as a PDK-1 inhibitor, is used as an apoptosis-promoting anticancer drug. However, whether OSU-03012 can inhibit VSMC proliferation and migration following PTCA remains unclear. In this study, we used A10 smooth muscle cells cultured in 10% FBS for stimulating proliferation and evaluated the inhibitory effects of OSU-03012 on cell proliferation and migration. The data demonstrated that OSU-03012 dose-dependently inhibited A10 cell proliferation examined by Trypan blue, MTT and morphological alteration assays, and inhibited the levels of proliferation-related proteins, proliferating cell nuclear antigen (PCNA), phosphorylated ERK examined by western blotting. Additionally, 10 mu M OSU-03012 also enhanced apoptosis examined using DAPI assay by regulating apoptosis-related proteins. Furthermore, compared with the control group, A10 cells treated with 10 mu M OSU-03012 showed a lower number of migrating cells examined by Boyden Chamber assay, and a dose-dependently reduced NFkB-dependent and interferon-stimulated response element (ISRE) promoter luciferase activities, implying the anti-migration and anti-inflammation effects of OSU03012. Taken together, this study provides insights into the pharmacological mechanisms of OSU-03012 in preventing smooth muscle cell proliferation, migration, and inflammation supporting the novel discovery of OSU-03012 as an adjuvant therapy for balloon injury-induced restenosis.
URI: http://dx.doi.org/10.1007/s11010-010-0531-5
http://hdl.handle.net/11536/32022
ISSN: 0300-8177
DOI: 10.1007/s11010-010-0531-5
期刊: MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume: 344
Issue: 1-2
起始頁: 81
結束頁: 89
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