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Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Research

Herbal compound triptolide synergistically enhanced antitumor activity of amino-terminal fragment of urokinase

Authors: Yuli Lin, Nana Peng, Jianping Li, Hongqin Zhuang, Zi-Chun Hua

Published in: Molecular Cancer | Issue 1/2013

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Abstract

Background

Urokinase (uPA) and its receptor (uPAR) play an important role in tumour growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumours. Targeting the excessive activation of this system as well as the proliferation of the tumour vascular endothelial cell would be expected to prevent tumour neovasculature and halt tumour development. The amino terminal fragment (ATF) of urokinase has been confirmed effective to inhibit the proliferation, migration and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Triptolide (TPL) is a purified diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook F that has shown antitumor activities in various cancer cell types. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to investigate the synergistic anticancer activity of TPL and ATF in various solid tumour cells.

Methods

Using in vitro and in vivo experiments, we investigated the combined effect of TPL and ATF at a low dosage on cell proliferation, cell apoptosis, cell cycle distribution, cell migration, signalling pathways, xenograft tumour growth and angiogenesis.

Results

Our data showed that the sensitivity of a combined therapy using TPL and ATF was higher than that of TPL or ATF alone. Suppression of NF-κB transcriptional activity, activation of caspase-9/caspase-3, cell cycle arrest, and inhibition of uPAR-mediated signalling pathway contributed to the synergistic effects of this combination therapy. Furthermore, using a mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumour growth by inhibiting angiogenesis as compared with ATF or TPL treatment alone.

Conclusions

Our study suggests that lower concentration of ATF and TPL used in combination may produce a synergistic anticancer efficacy that warrants further investigation for its potential clinical applications.
Appendix
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Metadata
Title
Herbal compound triptolide synergistically enhanced antitumor activity of amino-terminal fragment of urokinase
Authors
Yuli Lin
Nana Peng
Jianping Li
Hongqin Zhuang
Zi-Chun Hua
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-54

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