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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2014

Open Access 01-12-2014 | Research

Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model

Authors: Guo-Hua Deng, Jie Liu, Jie Zhang, Ying Wang, Xing-Chen Peng, Yu-Quan Wei, Yu Jiang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

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Abstract

Background

Sunitinib alone exhibits satisfactory efficacy in several mouse homografts and xenografts but unsatisfactory efficacy in many kinds of solid tumors in clinic. Different from animals, receiving a diagnosis of cancer impacts chronic stress on patients. Here, we examine whether norepinephrine (NE), one of the most potent stress related hormones, leads to the difference in the efficacy of sunitinib between clinical and preclinical trials.

Methods

The influence of NE on mouse melanoma B16F1 cells under sunitinib was evaluated in vitro and in vivo. The β-AR/cAMP/PKA (β-adrenoceptor/cyclic adenosine monophosphate/protein kinase A) signaling pathway was also evaluated in human lung adenocarcinoma cells.

Results

We found that NE upregulated the expression of VEGF, IL-8 and IL-6 in vitro and stimulated tumor growth in vivo, which was mediated by β-AR/cAMP/PKA signaling pathway and could be inhibited by propranolol, a β-blocker for hypertension for decades.

Conclusions

This research indicates exogenous norepinephrine attenuates the efficacy of sunitinib, and a combination of sunitinib and propranolol might be suggested as a new strategy in solid tumor in clinic.
Appendix
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Metadata
Title
Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model
Authors
Guo-Hua Deng
Jie Liu
Jie Zhang
Ying Wang
Xing-Chen Peng
Yu-Quan Wei
Yu Jiang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-33-21

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