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Inhibition Effect and Mechanism of YSY-01A, a Novel Proteasome Inhibitor, on Tumor-induced Angiogenesis
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
2013-08-01
DOI10.3724/SP.J.1206.2012.00398
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
WOS记录号WOS:000323456300008
项目编号2009ZX09301-010
资助机构12th Five Years Key Program-the Comprehensive Center for Drug Discovery and Development, Peking University
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53046
专题北京大学药学院
北京大学药学院_化学生物学系
北京大学药学院_分子与细胞药理学系
北京大学口腔医学院_急诊科
北京大学临床肿瘤学院_肿瘤放疗科
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
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.
APA Liu Jing-Tao.,Yuan Xia.,Xu Bo.,Ran Fu-Xiang.,Chu Ming-Ming.,...&Cui Jing-Rong.(2013).Inhibition Effect and Mechanism of YSY-01A, a Novel Proteasome Inhibitor, on Tumor-induced Angiogenesis.PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS,40(8),748-756.
MLA Liu Jing-Tao,et al."Inhibition Effect and Mechanism of YSY-01A, a Novel Proteasome Inhibitor, on Tumor-induced Angiogenesis".PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS 40.8(2013):748-756.
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