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Identification of Angiogenesis Inhibitors Using a Co-culture Cell Model in a
High-Content and High-Throughput Screening Platform
#MMPMID28922619
Li S
; Hsu CW
; Sakamuru S
; Zou C
; Huang R
; Xia M
SLAS Technol
2018[Jun]; 23
(3
): 217-225
PMID28922619
show ga
Angiogenesis is an important hallmark of cancer, contributing to tumor formation
and metastasis. In vitro angiogenesis models for analyzing tube formation serve
as useful tools to study these processes. However, current in vitro co-culture
models using primary cells have limitations in usefulness and consistency.
Therefore, in the present study, an in vitro co-culture assay system was
optimized in a 1536-well format for high-throughput screening using human
telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and
aortic endothelial cells. The National Center for Advancing Translational
Sciences (NCATS) Pharmaceutical Collection (NPC) library containing 2816 drugs
was evaluated using the in vitro co-culture assay. From the screen, 35 potent
inhibitors (IC(50) ?1 µM) were identified, followed by 15 weaker inhibitors
(IC(50) 1-50 µM). Moreover, many known angiogenesis inhibitors were identified,
such as topotecan, docetaxel, and bortezomib. Several potential novel
angiogenesis inhibitors were also identified from this study, including
thimerosal and podofilox. Among the inhibitors, some compounds were proved to be
involved in the hypoxia-inducible factor-1? (HIF-1?) and the nuclear factor-kappa
B (NF-?B) pathways. The co-culture model developed by using hTERT-immortalized
cell lines described in this report provides a consistent and robust in vitro
system for antiangiogenic drug screening.
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