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学科主题: 药学
题名:
Inhibition Effect and Mechanism of YSY-01A, a Novel Proteasome Inhibitor, on Tumor-induced Angiogenesis
作者: Liu Jing-Tao; Yuan Xia; Xu Bo; Ran Fu-Xiang; Chu Ming-Ming; Jia Xuan; Chen Yi-Xin; Wang Zhe; Li Run-Tao; Cui Jing-Rong
关键词: proteasome inhibitor ; angiogenesis ; human umbilical vein endothelial cells ; HT-29 cells ; high content screening ; YSY-01A
刊名: PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
发表日期: 2013-08-01
DOI: 10.3724/SP.J.1206.2012.00398
卷: 40, 期:8, 页:748-756
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: ENDOTHELIAL GROWTH-FACTOR ; PSEUDOLARIX ACID-B ; VASCULAR-PERMEABILITY ; PROLIFERATION ; APOPTOSIS ; MIGRATION
英文摘要:

Compound YSY-01A is a recently synthesized proteasome inhibitor. It has been proved for potent growth-inhibitory effect on tumor cells in previous studies. However, the effect of YSY-01A on tumor angiogenesis remains unclear. Our research aims to reveal the inhibition effect and mechanism of YSY-01A on tumor-induced angiogenesis. Firstly, we combined the Sulforhodamine B (SRB) assay and Transwell co-culture model to observe the inhibition of YSY-01A on human umbilical vein endothelial cells (HUVECs) proliferation induced by tumor cells (HT-29 cells). In succession, high content screening (HCS) assay was used to investigate effect of YSY-01A on NF-kappa B nuclear translocation in HT-29 cells. Finally, Western blot was used to measure the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in HT-29 cells inhibited by YSY-01A. To further determine mechanism of inhibition, SRB and HCS methods were used to investigate the effect of YSY-01A against HUVECs proliferation and motility, respectively. The results showed that YSY-01A could prohibit HUVECs proliferation induced by HT-29 cells in a concentration-dependent manner. Furthermore, YSY-01A significantly inhibited NF-kappa B nuclear translocation and reduced the expression of HIF-1 alpha and VEGF in HT-29 cells. Further investigation revealed concentration-dependent suppress of YSY-01A on HUVECs proliferation and motility without obvious cytotoxic effect. In conclusion, through proteasome inhibition, YSY-01A could down-regulate pro-angiogenesis factors expression in tumor cells and exhibit remarkable anti-angiogenesis activity on vascular endothelial cells.

语种: 中文
所属项目编号: 2009ZX09301-010
项目资助者: 12th Five Years Key Program-the Comprehensive Center for Drug Discovery and Development, Peking University
WOS记录号: WOS:000323456300008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53046
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Liu Jing-Tao,Yuan Xia,Xu Bo,et al. Inhibition Effect and Mechanism of YSY-01A, a Novel Proteasome Inhibitor, on Tumor-induced Angiogenesis[J]. PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS,2013,40(8):748-756.
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